Pending Policies - Medicine


Device Therapies for Gastroesophageal Reflux Disease (GERD)

Number:MED201.016

Effective Date:04-15-2018

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Transendoscopic therapy as a treatment for gastroesophageal reflux disease (GERD) may be considered medically necessary for transesophageal endoscopic gastroplasty also known as endoscopic gastroplication, fundoplication or transoral incisionless fundoplication [TIF] (e.g., StomaphyX™, EsophyX™) when meeting ALL the following criteria:

Age 18+;

Confirmed GERD by endoscopy, ambulatory PH, or barium swallow testing;

Greater than one year of GERD symptoms (reflux symptoms that occur 2 to 3 times per week);

History of daily proton pump inhibitor’s (PPI’s) for > six months;

GERD patients with body mass index (BMI) ≤ 35;

No Hiatal hernia >2 cm;

No Esophagitis LA (Los Angeles classification system) grade C or D;

No Barrett’s esophagus >2 cm;

Absence of achalasia and esophageal ulcer;

No altered esophageal anatomy that would prevent insertion of a device;

Absence of esophageal motility disorder; and

No previous history of failed antireflux surgery.

Transendoscopic therapy as a treatment for gastroesophageal reflux disease (GERD) is considered experimental, investigational and/or unproven for all other indications, including, but not limited to, the following device therapies:

Transesophageal radiofrequency to create submucosal thermal lesions of the gastroesophageal junction (e.g., the Stretta™ procedure);

Endoscopic submucosal injection or implantation of a prosthetic or bulking agent (e.g., Durasphere®, Gatekeeper™ Reflux Repair System); or

Endoscopic submucosal implantation of polymethylmethacrylate beads into the lower esophageal folds.

Description:

Gastroesophageal reflux disease (GERD) is a common disorder characterized by heartburn and other symptoms related to reflux of stomach acid into the esophagus. Nearly all individuals experience such symptoms at some point in their lives; a smaller number have chronic symptoms and are at risk for complications of GERD. The prevalence of GERD has been estimated to be 10% to 20% in the Western world, with a lower prevalence in Asia. (1)

The pathophysiology of GERD involves excessive exposure to stomach acid, which occurs for 1 of 3 reasons. There can be an incompetent barrier between the esophagus and stomach, either due to dysfunction of the lower esophageal sphincter (LES) or incompetence of the diaphragm. Another mechanism is abnormally slow clearance of stomach acid by the esophagus. A third mechanism is abnormally slow clearance of acid by the stomach. In this situation, delayed clearance leads to an increased reservoir of stomach acid and a greater tendency to reflux.

In addition to troubling symptoms, some patients will have more serious disease, which results in complications such as erosive esophagitis, dysphagia, Barrett esophagus, and esophageal carcinoma. Pulmonary complications may result from aspiration of stomach acid into the lungs and can include asthma, pulmonary fibrosis and bronchitis, or symptoms of chronic hoarseness, cough, and sore throat.

Guidelines on the management of GERD emphasize initial medical management. Weight loss, smoking cessation, head of bed elevation, and elimination of food triggers are all recommended in recent practice guidelines. (1) Proton pump inhibitor’s (PPI’s) have been shown to be the most effective medical treatment. In a Cochrane systematic review, PPIs demonstrated superiority to Histamine2-receptor (H2-receptor) agonists and prokinetics in both network meta-analyses and direct comparisons. (2)

The most common surgical procedure used for GERD is laparoscopic Nissen fundoplication. Fundoplication involves wrapping a portion of the gastric fundus around the distal esophagus to increase LES pressure. If a hiatal hernia is present, the procedure also restores the position of the LES to the correct location. Laparoscopic fundoplication was introduced in 1991 and has been rapidly adopted because it avoids complications associated with an open procedure.

Although fundoplication results in a high proportion of patients reporting symptom relief, complications can occur, and sometimes require conversion to an open procedure. Patients who have relief of symptoms of GERD after fundoplication may have dysphagia or gas-bloat syndrome (excessive gastrointestinal gas).

Due in part to the high prevalence of gastroesophageal reflux disease, there has been interest in creating a minimally invasive transesophageal therapeutic alternative to open or laparoscopic fundoplication or chronic medical therapy. This type of procedure may be considered natural orifice transluminal surgery.

Three types of transesophageal procedures have been investigated:

1. Transesophageal endoscopic gastroplasty (gastroplication, transoral incisionless fundoplication) can be performed as an outpatient procedure. During this procedure, the fundus of the stomach is folded, and then held in place with staples or fasteners that are deployed by the device. The endoscopic procedure is designed to recreate a valve and barrier to reflux.

2. Radiofrequency (RF) energy has been used to produce submucosal thermal lesions at the gastroesophageal junction. (This technique has also been referred to as the Stretta procedure). Specifically, RF energy is applied through 4 electrodes inserted into the esophageal wall at multiple sites both above and below the squamocolumnar junction. The mechanism of action of the thermal lesions is not precisely known but may be related to ablation of the nerve pathways responsible for sphincter relaxation or may induce a tissue-tightening effect related to heat-induced collagen contraction and fibrosis.

3. Submucosal injection or implantation of a prosthetic or bulking agent to enhance the volume of the lower esophageal sphincter has also been investigated. One bulking agent, pyrolytic carbon-coated zirconium oxide spheres (Durasphere®), is being evaluated. The Gatekeeper™ Reflux Repair System (Medtronic, Shoreview, MN) uses a soft, pliable, expandable prosthesis made of a polyacrylonitrile-based hydrogel. The prosthesis is implanted into the esophageal submucosa, and with time, the prosthesis absorbs water and expands, creating bulk in the region of implantation. U.S. Food and Drug Administration product code: DQX. Endoscopic submucosal implantation of polymethylmethacrylate beads into the lower esophageal folds has also been investigated. The Gatekeeper is no longer marketed in the U.S.

Regulatory Status

In 2007, EsophyX® (EndoGastric Solutions, Redmond, WA) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process for full-thickness plication (K071651). The predicate devices were the NDO Surgical Endoscopic Plication System K023234, Bard Endoscope Suturing System/Bard EndoCinch (K994290 and K003956), and EndoGastric Solutions StomaphyXTM endoluminal fastener and delivery system (K062875). A subsequent 2009 FDA clearance for EsophyX involved a device modification that was to “make the device easier to use, reduce cost of goods and improve manufacturability.” Subsequent FDA clearances occurred in 2014 and 2015. The 2015 patient indication states: The EndoGastric Solutions EsophyX Z Fastener Delivery Device with SerosaFuse Fasteners and Accessories is indicated for use in transoral tissue approximation, full thickness plication and ligation in the GI tract and is indicated for the treatment of symptomatic chronic gastroesophageal reflux disease in patients who require and respond to pharmacological therapy. It is also indicated to narrow the gastroesophageal junction and reduce hiatal hernia < 2cm in size in patients with symptomatic chronic gastroesophageal reflux disease. Note that these indications do not address patients with symptomatic chronic GERD who do not respond to pharmacologic therapy. In 2016, EsophyX® Z Device with SerosaFuse Fasteners was cleared for marketing (K160960) by the FDA through the 510(k) process for use in transoral tissue approximation, full thickness plication, ligation in the gastrointestinal tract, narrowing the gastroesophageal junction, and reduction of hiatal hernia of 2 cm or less in patients with symptomatic chronic GERD. FDA product code: ODE.

The Medigus SRS Endoscopic Stapling System (MUSE, Medigus Ltd) was cleared for marketing by the FDA through the 510(k) process in 2012 (K120299) and 2014 (K132151). MUSE is intended for endoscopic placement of surgical staples in the soft tissue of the esophagus and stomach to create anterior partial fundoplication for treatment of symptomatic chronic GERD in patients who require and respond to pharmacologic therapy. FDA product code: ODE.

In 2000, the CSM Stretta® System was cleared for marketing by the FDA through the 510(k) process for general use in the electrosurgical coagulation of tissue and is specifically intended for use in the treatment of GERD. Stretta® is currently manufactured by Mederi Therapeutics (Greenwich, CT). FDA product code: GEI. The FDA 510(k) documents Mederi submitted and dated December 2015 (K152317) indicate that the Stretta system is “intended for general use in the electrosurgical coagulation of tissue and intended for use specifically in the treatment of…GERD.” The predicate devices were earlier versions of the Stretta RF generator, electrodes, and Snowden-Pencer’s Nissen laparoscopic instrumentation.

Durasphere® is a bulking agent approved for treatment of urinary and fecal incontinence. Use of this product for esophageal reflux would be considered off-label use. The website of Carbon Medical Technologies states that Durasphere GR is an investigational device in the United States “intended to treat problems associated with GERD.”

Rationale:

This policy was based, in part, on a 2003 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment of transesophageal endoscopic treatments for gastroesophageal reflux disease (GERD) and a 2016 Assessment on transoral incisionless fundoplication. (2) Since the 2003 Assessment, this review has been updated periodically using the MEDLINE database. The most recent literature update was performed through April 2017. This medical policy will address procedures which are currently available for use in the United States.

The Agency for Healthcare Research and Quality (AHRQ) published a systematic review on management strategies for gastroesophageal reflux disease in 2005, which was updated in 2011. (3, 4) The 2005 comparative effectiveness review evaluated studies on the EndoCinch Suturing System, Stretta, Enteryx, and the NDO Plicator. (3) The 2011 update of the AHRQ report (4) excluded Enteryx and the NDO Plicator, because they were no longer available in the United States, and added the EsophyX procedure (endoscopic fundoplication), which was commercialized after the 2005 review. The 2011 AHRQ report concluded that for the 3 available endoscopic procedures (EndoCinch, Stretta, and EsophyX), effectiveness remains substantially uncertain for the long-term management of GERD. All of these procedures have been associated with complications; including dysphagia, infection/fever, and bloating, although bloating and dsyphagia are also adverse effects of laparoscopic fundoplication. (5) A 2015 review of endoscopic treatment of GERD noted that EndoCinch is no longer manufactured. (6)

Transoral Incisionless Fundoplication (TIF) (Esophyx®)

Patient Indications

The target population consisted of patients with chronic GERD eligible for TIF. This included patients with a hiatal hernia of 2 cm or less, and proven reflux either by endoscopy or ambulatory pH monitoring. Contraindications for TIF include a body mass index greater than 35 kg/m2, Barrett esophagus greater than 2 cm, esophageal ulcer, fixed esophageal stricture, and other gastric disorders (e.g., abnormal gastric motility). Patients may desire surgery if symptoms are not well controlled on medical therapy or, if controlled; they may desire to avoid chronic medical therapy.

In 2016, the Blue Cross and Blue Shield Center for Clinical Effectiveness published a Technology Assessment on transoral incisionless fundoplication for GERD using the EsophyX device. (7) Included were 4 randomized controlled trials (RCTs) from 2015 (described below), 3 studies that compared TIF to laparoscopic fundoplication, a multicenter registry, and case series with longer term follow-up to evaluate the durability of TIF. The Assessment concluded that the RCTs show better patient-reported outcomes with TIF compared with medical therapy at 6 months, although a fair proportion of TIF patients required resumption of proton pump inhibitor (PPI) therapy.

Randomized Trials Comparing TIF to Medical Therapy

We identified 4 RCTs comparing TIF to medical therapy. Trials varied by types of patients enrolled (controlled vs not controlled by a proton pump inhibitor (PPI), whether there was a sham control or not, and outcome measures employed (see Table 1). In general, patients included in these trials were eligible for surgery based on inadequate response to PPI therapy or desire to forgo long-term PPI therapy and a hiatal hernia of 2 cm or less. Patients were excluded if they had signs of severe GERD (e.g., severe grade esophagitis, esophageal dysmotility, extra-esophageal manifestations of GERD, and other complicating medical illnesses). The study by Hunter et al. was rated as good quality; the other studies were fair to poor (see Appendix Table 1). (6)

Table 1. Randomized Trials of TIF versus Medical Management, Selected Characteristics of Trials

Study

TIF:

CTRL n

Patient Symptoms or Other Characteristics

Comparator

Follow-Up, mo

Principal Clinical Outcome

Hunter et al. (2015)6

(RESPECT)

87:42

Troublesome regurgitation, not controlled on PPI

Sham + PPI

6

Relief of regurgitation without PPI in TIF group vs with PPI escalation in control group

Hakansson et al (2015)7

22:22

Controlled on PPI, run-in to confirm PPI dependence

Sham only

≥6

Time to resumption of PPI, percent needing PPI at 6 mo

Witteman et al. (2015)8

40:20

Controlled on PPI

Continued PPI

6

Mean GERD symptoms, percent with >50% improvement

Trad et al. (2015)9

(TEMPO)

40:23

Troublesome symptoms, not controlled on PPI

Maximum dose PPI

6

Elimination of daily symptoms other than heartburn

GERD: gastroesophageal reflux disease; PPI: proton pump inhibitor; TIF: transoral incisionless fundoplication.

Hunter et al. compared TIF plus placebo (n=87) to sham TIF plus PPI (n=42) in patients with troublesome regurgitation despite daily PPI therapy. (6) Troublesome regurgitation was defined as mild symptoms for 2 or more days a week or moderate-to-severe symptoms more than 1 day a week. The primary outcome was elimination of troublesome regurgitation at 6 months. Secondary outcomes included percent early failure (continued troublesome regurgitation at 3 months after increased medication), symptom scores, acid exposure, healing of esophagitis, and common side effects of treatment. Increases in medication (placebo or PPI depending on treatment group) were allowed at 2 weeks. At 3 months, patients with continued troublesome symptoms were declared early treatment failures, and failed TIF patients were given PPI and failed sham patients were offered TIF. For the primary outcome of elimination of troublesome regurgitation, the intention-to-treat analysis showed a higher success rate in the 67% (58/87) of TIF patients versus 45% (19/42) of sham patients (p=0.023) (see Table 2). The per-protocol analysis excluding 10 randomized patients not meeting original trial entry criteria showed similar findings. Other secondary outcomes (e.g., RDQ regurgitation score, RDQ heartburn score) showed no significant differences between treatments. Physiologic measurements such as number of reflux episodes, percent total time pH less than 4, and DeMeester score (a composite score of acid exposure based on esophageal monitoring) showed differences that were statistically significant.

The RCT by Hakansson et al. compared TIF (n=22) to sham only (n=22) in patients who were well controlled by chronic PPI treatment. (7) Although patients were controlled by chronic PPI treatment, trial eligibility required a run-in phase that required persistent GERD symptoms off PPI therapy and abnormal laboratory or endoscopic findings consistent with recurrence of GERD. Thus the expected outcome in the sham group was that, without PPI, GERD symptoms would eventually recur. The primary outcome was treatment failure, defined as the need for PPI treatment to control reflux symptoms when assessed at posttreatment office visits. Secondary outcomes included frequency and intensity of GERD symptoms, PPI usage, esophageal acid exposure, and side effects of treatment. Twenty-two patients were randomly assigned to each group. Kaplan-Meier curves of treatment failure showed a higher rate of treatment failure in the sham group than in the TIF group (p<0.001, log-rank test of time to treatment failure). The trial reported an average time in remission of 197 days in the TIF group versus 107 in the sham group, but it is unclear at what point these values are calculated (see Table 2). The follow-up time in the analysis must have been more than 6 months, because the maximum possible remission time at 6 months was 182, assuming 0 failures. Fifty-nine percent (13/22) of subjects in the TIF group were in remission at 6 months versus 18% (4/22) in the sham group (p=0.01).

Several secondary outcomes showed results consistent with more favorable outcomes in the TIF group. GERD symptoms, as assessed by the QOLRAD, only improved in the TIF group. A similar pattern emerged for symptoms as assessed by the GSRS. However, no formal statistical analysis was reported for between-group differences in these outcomes.

The RCT by Witteman et al. compared TIF (n=40) to continued PPI therapy (n=20) without sham controls in patients well-controlled with PPIs. (8) The trial was described as an equivalence trial, whose objective was to demonstrate that outcomes with TIF were not significantly worse than those with continued PPI therapy. The declared equivalence delta was 2 points measured on the GERD-HQRL. The trial population included patients well controlled with PPI therapy, but opting for an intervention over lifelong drug dependence. The primary outcome was treatment success, defined by an improvement of 50% or more on the GERD-HQRL. Secondary outcome measures included adverse events, esophageal acid exposure, number of reflux episodes, PPI usage, appearance of gastroesophageal valve, and healing of esophagitis. The trial was originally designed as a 2-center study, but this analysis was reported as an interim before the second center enrolled patients. Based on these results, the trial was terminated. Another critical aspect of the study is that baseline measurements of GERD symptoms were assessed after a 14-daycessation period of PPI therapy, thus allowing GERD symptoms to recur in many patients. Thus baseline GERD symptom levels do not represent patients’ steady-state levels of controlled symptoms. In the PPI therapy group, PPI therapy was stepped up or down as necessary during follow-up. In the TIF group, although patients did not initially start PPI therapy, they were allowed to use PPI in a similar step-up or step-down protocol as controls. At 6 months, 55% of TIF patients had more than 50% improvement in GERD symptoms versus 5% of patients on continued PPI therapy (p<0.001) (see Table 2). Mean change in GERD symptoms from baseline was consistent with this result (TIF, -14.1; control, -3.1; p<0.001). For this primary outcome, the noninferiority aspect of the trial is irrelevant, because the superiority result means that the noninferiority criterion was also met. Twenty-six percent of TIF patients resumed at least occasional PPI use by 6 months, and 100% of control patients remained on PPI therapy. With the exception of LES resting pressure, secondary physiologic and endoscopic outcome measures did not differ significantly between groups. TIF patients were followed beyond 6 months as a nonrandomized case series, with additional control patients who crossed over to have TIF. A total of 60 patients eventually underwent TIF, but there were losses to follow-up at 6 (7 patients) and 12 months (additional 8 patients). Although GERD symptoms remained improved over baseline (p<0.05), esophageal acid exposure did not differ significantly from baseline. At least occasional use of PPI increased between 6 months and 12 months, from 34% to 61%. Three TIF patients underwent fundoplication during this follow-up period. Endoscopy findings at 6 months and 12 months showed several findings indicating possible worsening of GERD in terms of esophagitis rating, Hill grade rating of the gastroesophageal valve, and size of hiatal hernia, but no formal statistical analysis of these changes was reported. Although this RCT met its principal end point at 6 months, and improvements in GERD symptoms appeared to be maintained to 12 months, due to findings observed between 6 months and 12 months in TIF patients, the authors concluded that “TIF is no[t an] equivalent alternative for PPIs in GERD treatment, even in this highly selected population.”

Trad et al. evaluated TIF (n=40) and maximum PPI therapy (n=23) without sham controls in patients with daily symptoms of regurgitation while on daily PPI therapy. (9) Eligible patients had had GERD for more than 1 year and a history of daily PPI use for more than 6 months. The control group was assigned to receive the maximum standard dose of PPI. The primary end point was elimination of daily troublesome GERD symptoms other than heartburn as assessed using a composite of 3 GERD symptom scales: the GERD-HRQL, RSI, and RDQ. It is unclear from the published article how the composite outcome was calculated, but it appears as if elimination of all symptoms except heartburn was required to achieve the end point. Another specific outcome mentioned was elimination of moderate-to-severe regurgitation with frequency reduced to 1 day a week or less, as assessed by the RDQ. Secondary end points included normalization of esophageal acid exposure, healing of esophagitis, PPI use, and serious adverse events. The trialists noted that some patients resumed PPI use after TIF, but did not describe any research protocol for this action. At 6-month follow-up, 39 of 40 TIF and 21 of 23 control patients were available for follow-up. Complete elimination of all daily troublesome GERD symptoms other than heartburn was achieved in 62% of patients in the TIF group and 5% in the control group (relative risk, 12.9; 95% confidence interval, 1.9 to 88.9; p<0.001) (see Table 2). Troublesome regurgitation was eliminated in 97% (29/30) of TIF patients who were off PPIs. This result appears to be misleadingly reported in the abstract of the article, where the denominator (patients off PPIs) is not mentioned. The trial reported that 90% (35/39) of patients in the TIF group had stopped taking PPIs, but the number of patients (n=35) is not the same as the previously reported denominator of 30 for patients off PPIs. However, esophageal acid exposure did not differ significantly between groups (TIF, 54%; PPI, 52%; p=0.914). At 6-month endoscopic assessment, healing or reduction in GERD symptoms was achieved in 90% of TIF patients and 38% in control patients (p=0.18), but not all patients were included in this comparison.

Table 2. Principal Clinical Outcomes of Randomized Trials Comparing TIF to Nonsurgical Treatment

Outcomes

TIF

Comparator

p

Hunter et al. (2015)6

TIF + placebo

Sham + PPI

Elimination of troublesome regurgitation

67%

45%

0.023

Change in RDQ regurgitation score

-3

-3

0.072

Change in RDQ heartburn score

-2.1

-2.2

0.936

Change in RDQ heartburn plus regurgitation score

-2.5

-2.4

0.313

Hakansson et al (2015)7

TIF

Sham

Days to remission

197

107

0.001

Change in median QOLRAD score at 6 mo

1.5

0.4

NR

Change in median GSRS score at 6 mo

4

1.4

NR

Percent off daily PPI therapy at 6 mo

59%

18%

0.01

Witteman et al. (2015)8

TIF

Continued PPI

Mean change in GERD-HRQL

-14.1

-3.1

<0.001

Percent >50% improvement GERD-HRQL

55%

5%

<0.001

Change in percentage with esophagitis

-19%

-20%

>0.05

Trad et al. (2015)9

TIF

Maximum dose PPI

Elimination of symptoms other than heartburn

62%

5%

0.001

Daily PPI use

8%

NR

-

Change in GERD-HRQL score

-21.1

-7.6

<0.001, <0.001a

GERD-HRQL Heartburn score

-14

-5.2

<0.001, <0.001a

RSI score

-17.4

-3.0

<0.001, 0.205a

GERD-HRQL: Gastroesophageal Reflux Disease Health-Related Quality of Life; GSRS: Gastrointestinal Symptom Rating Scale; NR: not reported; PPI: proton pump inhibitor; QOLRAD: Quality of Life in Reflux and Dyspepsia; RDQ: Reflux Disease Questionnaire; RSI: Reflux Symptom Index; TIF: transoral incisionless fundoplication.

a Within-group p values calculated separately for TIF and control, no between group analysis.

Safety and Adverse Event Reporting in the Randomized Trials

The RCT by Hunter et al. reported that, with the exception of postoperative epigastric pain, complications and adverse effects did not different between groups. (10) One patient in the TIF group and 2 patients in the sham group developed de novo dysphagia.

The RCT by Hakansson reported rates of dysphagia, bloating, flatulence, and left shoulder pain that did not differ significantly different between groups. (11) Postoperative epigastric pain was much greater in the TIF group (45% vs 5%, p=NS). One TIF patient had dysphagia, which lasted for 3 months, but did not require intervention.

In the trial by Witteman et al., 1 TIF patient developed pneumoperitoneum perioperatively. Three TIF patients developed pneumonia, 1 of whom required hospital admission. (12) Side effects of fundoplication (e.g., pain, flatulence, bloating, diarrhea) did not occur in TIF patients, as assessed by the GSRS.

In Trad et al., the only adverse events mentioned were in 2 TIF patients who required an extra day in the hospital, 1 due to postoperative dizziness and nausea and 1 due to an allergic reaction. (13)

Studies Comparing TIF to Laparoscopic Fundoplication

Three studies have compared TIF to laparoscopic fundoplication. One was an RCT (14) and 2 were nonrandomized comparative studies. (15,16)

The RCT by Svoboda et al. (14) compared 34 patients receiving TIF to 18 patients receiving fundoplication. Patients were enrolled if they had chronic GERD symptoms, abnormal esophageal acid exposure test results, partial response to PPI therapy, hiatal hernia less than 2 cm, and no findings associated with severe esophagitis and/or complications. At 12-month follow-up, 26 (76%) of 34 TIF patients and 14 (78%) of 18 fundoplication patients were available. There was no declared principal outcome of the study. GERD-HRQL scores improved in both groups to a similar extent at 3 months and 12 months (12-month scores, 6.6 for TIF vs 6.7 for fundoplication; p=0.7). In terms of the percentage of subjects with 50% or more improvement in GERD-HRQL scores at 12 months, results were similar (68% for TIF vs 71% for fundoplication; p=0.397. Fifty percent of TIF subjects were off PPI at 12 months versus 71% of fundoplication subjects (p=0.2). Four serious adverse events occurred: 1 in the TIF group and 3 in the fundoplication group. The adverse event in the TIF group did not occur in a patient who had the procedure using EsophyX. The adverse events in the fundoplication group were unrelated to surgery.

A nonrandomized study by Frazzoni et al. compared 10 patients undergoing TIF to 10 patients undergoing laparoscopic fundoplication. (15) Eligible patients had persisting symptoms despite at least 4 weeks of high-dose PPI therapy. Patients with signs of severe esophagitis and extra-esophageal manifestations of GERD were excluded. Patients selected which treatment they wanted. The principal clinical outcome was not specifically declared, but appeared to be a categorical rating (range, 0-3) of heartburn and regurgitation symptoms. Changes in categorical rating of symptom remission were then collapsed into 2 categories, total and subtotal remission (final score of 0 or a 2-point improvement), and partial and no remission (no change in score or a 1-point improvement), based on initial and final score. Assessments of acid exposure and esophageal function at postprocedure endoscopy, manometry, and impedance pH monitoring were also planned. At baseline, patients had similar levels of acid exposure and reflux as assessed by preprocedure endoscopy and manometry. In terms of clinical outcomes assessed at 3 months, 7 patients undergoing TIF reported only partial/no symptom remission versus 0 patients undergoing fundoplication (p=0.003). Mild dysphagia was reported by 2 patients after fundoplication and 1 patient after TIF. Two patients reported epigastric bloating after fundoplication. Several measures of GERD as assessed by manometry and impedance pH monitoring showed greater improvement in the fundoplication group than in the TIF group. This study reported that TIF is less effective than fundoplication in improving symptoms of GERD. Adverse perioperative events were not described.

A nonrandomized study by Toomey et al. compared 20 patients undergoing TIF, 20 patients undergoing Nissen fundoplication, and 20 patients undergoing Toupet fundoplication. (16) The trialists stated that age, body mass index, and preoperative DeMeester score were controlled. The indications for each procedure resulted in imbalance in important patient characteristics. Patients with abnormal esophageal motility underwent Toupet fundoplication. Only patients who had a hiatal hernia of 2 cm or less were offered TIF. Due to these selection criteria, at baseline, 15% of the TIF group had a hiatal hernia versus 65% and 55% of the 2 fundoplication groups. Another incidental difference in baseline characteristics was the proportion of patients undergoing a reoperation for GERD: 25% in the TIF group versus 5% and 5% in the 2 fundoplication groups. The principal study outcomes were not specified, but up to 16 measures of various symptoms (rated 0 to 10 for severity and frequency) were assessed at baseline and follow-up. Evaluation of symptom outcomes occurred at an unstated unknown time postsurgery. Results are displayed in the published article as preoperative and postoperative median values of various symptoms’ severity or frequency for each procedure. It appears as if, qualitatively, most measures of symptoms decreased to low levels (median ranges, 0-2) after all procedures. Quoting from the article: “… there was significant amelioration of symptom frequency and severity and with no significant difference among patients who underwent TIF or … Nissen or Toupet fundoplications.” (16) The study reported the percentage of patients in each group with symptoms less than once per month (83% of TIF patients, 80% of Nissen fundoplication patients, 92% of Toupet fundoplication patients; p=0.12). Patient-rated satisfaction was 67% for TIF, 86% for Nissen fundoplication, and 92% for Toupet fundoplication (p value not reported), but described as “similar.” Adverse events were not reported for procedures.

Studies Assessing the Durability of TIF

In 2009, Cadiere et al. reported 2-year results of a small case series of patients undergoing TIF. (17) Of the original series of 19 patients, 14 patients were assessed at 2 years. Two of the excluded patients underwent additional surgical treatment. At 2 years, median GERD-HRQL scores improved from 17 to 7 (p=0.004), with 64% having more than 50% reduction in GERD-HRQL scores. Seventy-one percent of patients were not taking daily PPI therapy at 2 years. Twenty-nine percent (4/14) were considered “cured” when defined as no heartburn, no daily PPI use, no hiatal hernia, and no esophagitis. Fifty percent (7/14) were considered “in remission” when defined as reduced heartburn, reduced hiatal hernia, or reduced esophagitis, but requiring occasional use of PPIs. This study did not report 1 year outcomes, so changes in outcome between 1 and 2 years are unknown.

In 2012, Testoni et al. reported 2-year outcomes for a case series of patients undergoing TIF. Of the original series of 42 patients, 26 patients had follow-up data at 24 months. (18) Four patients had additional surgical treatment between 12 months and 24 months, and are not included in the analysis. GERD symptoms as measured by the GERD-HRLQ and GERD-QUAL scores were significantly improved from baseline at all time points. However, these scores reverted toward baseline values at each subsequent time point, but this change was not evaluated with formal statistical testing. PPI use increased over time between 6 months and 24 months; defining responders as those who completely stopped PPI use, the percentage of responders decreased from 60% (21/35) at 6 months to 42% (11/26) at 24 months (p=0.2)

In 2014, Muls et al. reported 3-year outcomes for a case series of patients undergoing TIF. (19) Of 86 patients in the original case series; 1- and 3-year follow-ups were available on 66 and 54 patients, respectively. Twelve patients underwent additional surgical treatment between 1 and 3 years; they were included in an intention-to-treat analysis and assigned the worst possible values for all outcomes. This study reported outcomes at baseline, 1 year, and 3 years on the same patients, and permitted the best examination of change in outcomes between the 2 time points. Compared to baseline values, median GERD-HRQL scores improved at both 1- and 3-year follow-ups. The percentage of patients whose scores decreased by 50% or more was 75% at 1 year and 65% at 3 years. The percentage of patients reporting satisfaction was 68% at 1 year and 58% at 3 years. The percentage of patients not using daily PPI decreased from 86% at 1 year to 61% at 3 years. The percent of patients not using any PPI decreased from 70% at 1 year to 52% at 3 years. None of these differences in outcome between 1 year and 3 years were formally evaluated with statistical significance testing.

In 2014, Bell et al. reported 2-year outcomes of TIF from a multicenter registry. Of 127 patients enrolled, 100 patients had 2-year follow-up data. (20) Another 8 patients who underwent additional surgical treatment between 6 months and 24 months were included in the analysis but designated as treatment failures and assigned pretreatment values for all outcomes. Findings at 12 months (n=123) and 24 months (n=108) showed improvements in all measures of GERD symptoms compared to baseline (p<0.001 for all symptom measures). Values of some specific GERD symptoms between 12 months and 24 months generally showed no change or some movement back toward baseline, but there was no statistical testing for change between 12 months and 24 months. Some scores showed reversion toward baseline values. Among 98 patients who used PPI daily at baseline, 70% no longer used it daily.

In 2015, Testoni et al. reported outcomes for patients undergoing TIF followed for up to 6 years. (21) Of 49 patients undergoing TIF, variable numbers of patients are reported at each time point. Four patients are mentioned as having undergone additional surgical treatment and 1 is mentioned as having been lost to follow-up. At 2 years and 3 years after TIF, GERD-HRQL and GERD-QUAL scores were improved compared to baseline. However, GERD-QUAL scores at 3 years assessed while patients were off PPIs are closer to baseline than the 2-year scores (baseline score, 114; 1-year score, 71; 3-year score, 80), but these differences were not formally statistically evaluated. Defining complete responders as those who completely stopped using PPIs at 1, 2, 3, 4, 5, and 6 years, complete response was observed in 51%, 56%, 53%, 46%, 32%, and 36%, respectively. The proportion of subjects who remained on their baseline dose of PPI was roughly constant throughout the period (range, 14.3%-21.1%) without the appearance of a temporal trend. The increase in use was primarily due to increases in low-dose PPI.

ECRI

ECRI prepared a Product Brief in February 2016 relevant to EsophyX (EndoGastric Solutions, Inc., Redmond, WA, USA). (42) PubMed, EMBASE, and selected web-based resources were searched for documents relevant to and published between January 1, 2011, and February 10, 2016. One systematic review, 1 cost-effectiveness analysis, 4 randomized controlled trials (RCTs) reported in 6 publications comparing EsophyX to sham therapy as well as 2 nonRCTs comparing EsophyX to active treatments, and 14 case series. The controlled studies reported on 389 patients. Overall, results were mixed on how EsophyX compares to other treatments. Some analyses favored EsophyX; others favored laparoscopic fundoplication.

In a 2016 American Gastroenterological Association (AGA) Technology Coverage Statement on Minimally Invasive Surgical Options for Gastroesophageal Reflux Disease, the following was noted: “The three?year plus evidence (42) is sufficient to demonstrate sustainable improvement in health outcomes, symptom relief, decrease in PPI utilization and improvement in esophageal pH with transoral fundoplication. The selection criteria for transoral fundoplication includes GERD patients with BMI ≤ 35, hiatal hernia ≤ 2 cm, esophagitis LA grade A or B, Barrett’s esophagus ≤ 2cm, and absence of achalasia and esophageal ulcer. This option should be considered in patients not responding to PPI therapy (symptoms of regurgitation) who have documented objective evidence of GERD (pathologic acid exposure on pH testing (both off and on medication) or esophagitis.”

Section Summary: Transoral Incisionless Fundoplication (EsophyX)

To determine whether TIF for treating GERD improves the net health outcome, studies were selected that compared TIF to medical therapy, TIF to laparoscopic fundoplication, and studies that assessed long-term TIF outcomes.

For individuals who have GERD who receive TIF, the evidence comparing TIF and medical therapy includes 4 randomized controlled trials (RCTs). These trials varied in selection criteria, comparators, and outcome measures. All studies assessed GERD symptom outcomes at 6 months. One study was rated as good and the others were fair to poor using U.S. Preventive Services Task Force criteria. All 4 trials met their designated end points, showing a treatment effect of TIF relative to medical therapy. In all studies, at least a majority of subjects were able to stay off PPI treatment for the duration of the trial.

For individuals who have GERD who receive TIF, the evidence comparing TIF and fundoplication includes 1 RCT and 2 nonrandomized studies. The RCT included subjects undergoing TIF with a different device. It showed no statistically significant differences between TIF and fundoplication. One nonrandomized study showed that TIF was much less effective than fundoplication. In the third nonrandomized study, indications for TIF and fundoplication varied, resulting in patients with different characteristics undergoing the different procedures. This study showed no statistically significant differences in outcomes between TIF and fundoplication.

For individuals who have GERD who receive TIF, the evidence evaluating durability of treatment effects includes five case series reported patient outcomes at 2 years or beyond. Studies varied in the proportion of patients followed long term. All studies showed GERD symptoms had improved at the last follow-up over baseline. Only 2 studies reported outcomes at 3 years or beyond. They showed increases in PPI therapy use beyond 3 years and some loss of TIF treatment effectiveness. These findings comparing outcomes at different follow-up times were not formally analyzed.

All 4 RCTs have shown GERD symptoms improve with TIF compared to medical therapy, analysis of outcomes was limited to 6 months postprocedure.

Transesophageal Radiofrequency (i.e., Stretta Procedure)

The available evidence consists of a meta-analysis and 4 small RCTs, all 4 of which include a sham placebo control, along with numerous uncontrolled case series.

Systematic Review and Meta-Analyses

A systematic review and meta-analysis was published by Lipka et al. in 2014. (22) Four RCTs with a total of 165 patients were included in the meta-analysis. (23-26) 3 trials compared Stretta versus sham, and 1 trial compared Stretta with PPI therapy. The overall quality of evidence was considered to be very low with a high risk of bias. The pooled results showed no significant difference between Stretta and sham or PPI management for the measured outcomes. The mean difference (control minus Stretta) in the percent time that pH was less than 4 was 1.56 (95% confidence interval [CI], -2.56 to 5.69). The mean difference for esophageal sphincter pressure was -0.32 mm Hg (95% CI, -2.66 to 2.02). The mean difference in HRQL from 2 studies was -5.24 (95% CI, -12.95 to 2.46). The relative risk ratio for the ability to discontinue PPIs was 0.87 (95% CI, 0.75 to 1.00). This meta-analysis is limited by heterogeneity in the included studies, which may be due to small sample sizes, differences in measures, and differences in follow-up time.

A 2012 meta-analysis by Perry et al. included 20 studies (2 RCTs, 18 case series) with a total of 1441 patients. (27) This review analyzed the within-subjects results following treatment only. The control groups of available clinical trials were not included for comparison. Analysis of the 9 studies (525 patients) that reported subjective heartburn scores showed a significant decrease from 3.55 to 1.19 at a mean of 24.1 months. Analysis of the 9 studies (433 patients) that reported GERD-HRQL scores showed an improvement from 26.11 to 9.25 at a mean follow-up of 19.8 months. Analysis of the 6 studies (299 patients) that reported SF-36 Physical Component Summary scores showed an improvement from 36.45 to 46.12 at a mean follow-up of 9.5 months. For the 11 studies that measured esophageal pH, significant improvements were found in the Johnson-DeMeester score (44.37 to 28.53), the esophageal acid exposure time (10.29% to 6.51%), and lower esophageal sphincter pressure (16.54 to 20.24). This metaanalysis is limited by the inclusion of lower quality studies and by the analysis, which only examined within-subject differences and did not include between-subjects differences, as reported in the RCTs.

A 2017 meta-analysis included twenty-eight studies (4 RCTs, 23 cohort studies, and 1 registry) representing 2468 unique Stretta patients. The (unweighted) mean follow-up time for the 28 studies was 25.4 [14.0, 36.7] months. The pooled results showed that Stretta, reduced (improved) the health-related quality of life score by -14.6 [-16.48, -12.73] (P < 0.001). Stretta also, reduced (improved) the pooled heartburn standardized score by -1.53 [-1.97, -1.09] (P < 0.001). After Stretta treatment, only 49% of the patients using proton pump inhibitors (PPIs) at baseline required PPIs at follow-up (P < 0.001). The Stretta treatment reduced the incidence of erosive esophagitis by 24% (P < 0.001) and reduced esophageal acid exposure by a mean of -3.01 [-3.72, -2.30] (P < 0.001). Lower esophageal sphincter (LES) basal pressure was increased post Stretta therapy by a mean of 1.73 [-0.29, 3.74] mmHg (P = NS). The authors note that the meta-analysis demonstrated that the Stretta procedure significantly reduced the use of PPIs while improving esophageal acid exposure time, heartburn symptoms, and HRQL. The observed 24% reduction in erosive esophagitis incidence approached, but did not reach, statistical significance under the random effects (P = 0.08), but did reach statistical significance under fixed effects (P < 0.001). There was no significant effect on LES basal pressure. Also, the authors note that Stretta appears to be efficacious in improving both objective and subjective clinical endpoints.

RCTs Comparing Transesophageal Radiofrequency vs Sham

The 2003 BCBSA TEC Assessment included 1 randomized, sham-controlled trial by Corley et al. (25) This trial enrolled patients with symptoms at least partially responsive to PPIs, a pH study showing abnormal acid exposure, and the usual exclusions including severe esophagitis or significant anatomic defect. The sham procedure involved balloon inflation but no needle deployment or energy delivery. A total of 64 patients were randomized and partial or complete 6-month follow-up data were available on 56 patients. The results of this trial were inconsistent. Although improvement in heartburn symptoms, quality of life, and general physical quality of life was observed in the active treatment group compared with the sham group, there were no differences in medication usage and esophageal acid exposure. Thus in terms of the objective measures of GERD, the findings are equivocal. The large proportion of sham-treated patients successfully reducing medication use points to possible placebo effect of the procedure.

Aziz et al. reported a 12-month randomized, double-blind, sham-controlled trial in 36 patients whose GERD was controlled with PPIs. (24) Patients were randomly assigned to receive RF, which could be repeated if there was a less than 75% improvement in GERD-HRQL scores at 4 months, or a sham procedure. At 12 months, 17% of patients in the single-session group, 50% in the double-session group, and 0% of the sham-treated patients had discontinued PPIs. Statistically significant improvements in GERD-HRQL were observed in all 3 treatment groups: In the single-session RF group, GERD-HRQL scores improved from a mean of 30 at baseline to 14 posttreatment; in the double-session RF group, GERD-HRQL scores improved from 31 to 11; and in the sham group, GERD-HRQL scores improved from 30 to 25. Mean total esophageal acid exposure time decreased in the active treatment groups (from 9.4 to 6.7 minutes in the single-session group [p<0.01], from 8.8 to 5.2 minutes in the double-session group [p<0.01]) but not in the sham group. The clinical relevance of these changes is uncertain. Serious adverse events occurred in 3 patients following RF treatment; 1 patient developed pneumonia and in 2 patients developed prolonged gastroparesis.

Arts et al. reported a double-blind randomized crossover study of Stretta and sham treatment in a small trial with 22 GERD patients. (23) The initial sham treatment in 11 patients did not affect any of the outcome measures. Three months after the RF procedure, the symptom score was significantly improved (14.7 to 8.3), and gastroesophageal junction compliance was significantly decreased (17.8 vs 7.4 mL/mm Hg). The quality-of-life score for bodily pain improved from 49.5 to 24.0. No changes were observed in PPI use, esophageal acid exposure, or lower esophageal sphincter pressure after RF. The decrease in compliance of the gastroesophageal junction was reversed by a smooth muscle relaxant, suggesting that the effect of RF on gastroesophageal junction compliance was not due to fibrosis.

In an unblinded randomized trial by Coron et al. a total of 43 PPI-dependent GERD patients either continued the effective dose of their PPI or received the RF procedure (Stretta). (26) At 6 months, significantly more patients in the treatment group were able to discontinue or decrease their PPI use by at least 50% than in the control group, a difference that was not maintained at 12 months. Some authors have suggested that PPI discontinuation rather than dose reduction is a more meaningful outcome measure. In this study, the number of patients able to discontinue PPI medication did not differ between groups.

Controlled Trials Comparing Transesophageal Radiofrequency Versus Laparoscopic Fundoplication

In 2015, Liang et al. reported a prospective comparison of laparoscopic Toupet fundoplication (n=80) versus the Stretta procedure (n=85). (28) Of the 165 patients treated, 125 (76%) completed the 3-year follow-up (65 fundoplication, 60 Stretta) and were included in the analysis. Although the 2 groups were comparable in symptoms at baseline, 9 patients in the Stretta group had revised treatment and were not included in the final symptom scores. A similar percentage of remaining patients in the 2 groups achieved complete PPI independence (laparoscopic fundoplication: 72.3% vs Stretta: 68.3%; p=.627) and had similar improvements in belching, hiccup, cough, and asthma. The Stretta procedure was less effective than laparoscopic fundoplication in improving symptoms of heartburn (mean improvement, 2.53 vs 4.05; p=0.01), regurgitation (mean improvement, 2.41 vs 4.03; p=0.004), and chest pain (mean improvement, 2.96 vs 5.50; p=0.005). Significantly more patients in the Stretta group underwent reoperation (11.8% vs 0%; p=0.006), while more patients in the fundoplication group complained of bloating (6.2% vs 0%, p=0.120), but these differences were not statistically significant. This study lacked randomization and had high loss to follow-up. While symptom scores were comparable at baseline, the study may have been subject to selection bias related to treatment choice of, which affected baseline differences for other variables.

Durability of Transesophageal Radiofrequency

Ten-year follow-up after the Stretta procedure was reported by Noar et al. (29) All patients had daily recurring symptoms of heartburn and regurgitation despite twice-daily PPI use. Of a total of 217 patients treated, 149 had reached 10-year follow-up. Of those, 50 were lost to follow-up (11 were deceased), resulting in 99 patients in the cohort. Of the 99 patients with 10-year follow-up, 72% showed normalization of GERD-HRQL scores, 64% had a 50% or greater reduction in PPI use, and 41% eliminated PPIs completely. Comparison of results out to 4 years in the total cohort (n=217) and completers only (n=99) showed no evidence of bias associated with non-completers. In a subset of 51 patients who underwent repeat endoscopy at 10 years or later, only 5 of the 33 patients who had dysplasia at study entry had remaining metaplasia. In the 18 patients without metaplasia at study entry, there was no change in esophageal histology.

A 5-year prospective observational study with 138 of 152 patients was reported by Liang et al. in 2014. (30) Symptoms of heartburn, regurgitation, chest pain, cough, and asthma were all decreased significantly compared with baseline (p<0.001). More patients were completely off PPI therapy at 5 years (42.8%) than at 6 months (27.5%). Bloating was observed in 12 (8.7%) of patients after the Stretta procedure. No reoperations were reported.

ECRI

ECRI prepared a Product Brief in February 2016 relevant to the Stretta System (Mederi Therapeutics, Inc.) for treating GERD. (41) Eight documents were identified reporting on Stretta in 2,267 patients with GERD: 2 systematic reviews, 1 randomized controlled trial (RCT), 2 nonrandomized comparative studies, and 2 case-series studies. Results from studies on the Stretta procedure’s effectiveness are mixed. One systematic review reporting only on RCTs (n = 165) found no significant differences between Stretta and a sham procedure or PPI therapy in improving GERD symptoms. The other systematic review (n = 1,441), which included RCTs and uncontrolled cohort studies, reported that Stretta significantly improved reflux symptoms. Results from 1 small RCT (n = 22) published since the time of the meta-analyses, 2 non-RCTs (n = 223), and 2 case series (n = 307) suggest that Stretta may be safe; these studies also reported improvements in GERD, and some patients eventually achieved freedom from need for PPIs. Large, longer-term RCTs are needed to determine the efficacy of Stretta compared to other GERD procedures and PPI therapy. Two ongoing clinical trials are assessing Stretta for treating GERD. These trials are estimated to end in December 2018. One trial is an RCT but is reporting only short-term (six-month) outcomes.

ECRI prepared a Product Brief in May 2017. (41) While the ECRI product brief appears to indicate that the evidence is somewhat favorable regarding Stretta, it concludes the procedure is less effective than laparoscopic Nissen fundoplication, and notes that studies comparing Stretta to other minimally invasive procedures for GERD are needed.

Section Summary: Transesophageal Radiofrequency (i.e., Stretta Procedure)

Four small RCTs report improvements in symptoms and quality of life following treatment with RF energy, however, a meta-analysis of these same studies found no significant improvement in outcomes. Nonrandomized studies show maintenance of efficacy at 3 to 10 years, although symptom relief with RF energy may be lower than with fundoplication and reoperations greater.

Published reviews of current literature are conflicted in their recommendations of Stretta in the management of GERD. There appears to be a lack of standardization of outcome measures and heterogeneity of assessment tools in all studies. Studies comparing Stretta to other minimally invasive procedures for GERD are needed.

Injection/Implantation of Prosthetics or Bulking Agents

Durasphere

The available evidence for this device consists of 1 case series. One open-label pilot study (18) of 10 GERD patients injected Durasphere (Carbon Medical Technologies, St. Paul, MN), a bulking agent approved for treatment of urinary and fecal incontinence, at the gastroesophageal junction. At 12 months, 7 patients (70%) discontinued all antacid medication completely. No erosion, ulceration, or sloughing of material was noted at any injection site.

Gatekeeper Reflux Repair System

The available evidence for this device consists of 1 RCT. An industry-funded sham-controlled single-blind multicenter study randomized 118 patients into Gatekeeper (n=75) or sham (n=43) treatment. (19) An additional 25 patients were treated as lead-ins during the initial training of investigators and included only in the safety analysis. The patients were implanted initially with 4 Gatekeeper prostheses. At 3 months, 44% of implanted patients received retreatment with up to 4 additional prostheses due to unsatisfactory symptom control. The primary safety end point was reduction in serious device- and procedure-related adverse device effects, compared with a surgical procedure composite complication rate of 15%. Four serious adverse events were reported (2 perforations, 1 pulmonary infiltrate related to a perforation, 1 severe chest pain). The primary efficacy end point was reduction in heartburn symptoms using the GERD-HRQL questionnaire. Planned interim analysis after 143 patients were enrolled found that heartburn symptoms and esophageal acid exposure had improved significantly in both the Gatekeeper and sham groups at 6 months, but there was no significant difference between the 2 groups. The study was terminated early due to a lack of efficacy.

Polymethylmethacrylate Beads

The available evidence for this device consists of 1 case series. A 2001 publication on transesophageal submucosal implantation of polymethylmethacrylate beads consisted of a case series of 10 patients with GERD who were either refractory to or dependent on PPIs. (20) While a significant decrease in symptom scores was noted at posttreatment follow-up (time not specified), the small number of patients and lack of long-term follow-up preclude scientific analysis. No additional studies have been identified evaluating this treatment option.

Ongoing and Unpublished Clinical Trials

Table 2. Summary of Key Trials

NCT No.

Trial Name

Planned Enrollment

Completion Date

NCT01682265

Stretta in Reflux Uncontrolled by Intake of Inhibitors of Protons Pump (IPP)-The SIRUP Trial-Multicentric, Randomized, Double Blind, Prospective Study

500

June 2018

NCT01118585a

Prospective Outcome Evaluation of Transoral Incisionless Fundoplication (TIF) for the Treatment of Gastroesophageal Reflux Disease (GERD): The TIF Registry

60

March 2017

NCT02211105

Laparoscopic Nissen Fundoplication (LNF) Surgery Versus Transoral Incisionless Fundoplication (TIF): Anti- Reflux Treatment Registry

500

December 2018

NCT: national clinical trial.

a Denotes industry-sponsored or cosponsored trial.

Practice Guidelines and Position Statements

American College of Gastroenterology (ACG)

Updated guidelines released by the American College of Gastroenterology in 2013 state that the usage of current endoscopic therapy or transoral incisionless fundoplication (TIF) cannot be recommended as an alternative to medical or traditional surgical therapy (conditional recommendation, moderate level of evidence). (21)

American Society for Gastrointestinal Endoscopy (ASGE):

In 2015, ASGE published guidelines on endoscopic procedures for GERD. (40) ASGE gave a number of recommendations based on moderate or high-quality evidence for the endoscopic evaluation of GERD. ASGE suggested, based on low-quality evidence, that antireflux therapy be considered for selected patients with uncomplicated GERD.

The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES):

SAGES provided evidence-based guidelines on endoluminal treatments for GERD in 2013. (22) SAGES gave a weak recommendation based on low-quality evidence for the EsophyX procedure, stating that long-term data are not yet available and that further studies are required to define optimal techniques and most appropriate patient selection criteria, and to further evaluate device and technique safety. SAGES gave a strong recommendation based on high-quality evidence that Stretta is considered appropriate therapy for patients being treated for GERD who are 18 years of age or older, who have had symptoms of heartburn, regurgitation, or both for 6 months or more, who have been partially or completely responsive to antisecretory pharmacologic therapy, and who have declined laparoscopic fundoplication.

The American Society of General Surgeons (ASGS)

The ASGS issued a position statement on transoral fundoplication in 2011 stating that “ASGS supports the use of transoral fundoplication by trained General Surgeons for the treatment of symptomatic chronic gastroesophageal reflux disease (GERD) in patients who fail to achieve satisfactory response to a standard dose of Proton Pump Inhibitor (PPI) therapy or for those who wish to avoid the need for a lifetime of medication dependence. (23)

The American Gastroenterological Association (AGA)

The 2008 the Medical Position Statement of the American Gastroenterological Association (24) makes no recommendation for or against “the use of currently commercially available endoluminal antireflux procedures in the management of patients with an esophageal syndrome” based on insufficient evidence (grade insufficient).

The National Institute for Health and Care Excellence (NICE)

The NICE of the National Health Service of Great Britain issued updated interventional procedure guidance in 2013 on endoscopic radiofrequency treatment for GERD, concluding: “The evidence on the safety of endoscopic radiofrequency ablation for gastro-esophageal reflux disease is adequate in the short and medium term but there is uncertainty about longer-term outcomes. With regard to efficacy, there is evidence of symptomatic relief but objective evidence on reduction of reflux is inconclusive. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research. (25) The reviewing committee noted “concern on the part of some specialists about the possibility that symptoms may improve as a result of denervation caused by the procedure; if that were the case then failure to recognize and treat reflux might lead to complications in the long term.”

NICE issued guidance in 2011 on endoluminal gastroplication for GERD, concluding that “The evidence on endoluminal gastroplication for gastroesophageal reflux disease raises no major safety concerns. Evidence from a number of RCTs [randomized controlled trials] shows a degree of efficacy in terms of reduced medication requirement in the short term, but changes in other efficacy outcomes are inconsistent, and there is no good evidence of sustained improvement in esophageal pH measurements. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research.” (26)

The 2004 Guidance from NICE on bulking agents for GERD found that “Current evidence on the safety and efficacy of endoscopic injection of bulking agents for gastro-esophageal reflux disease does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research. (27)

Summary on Transendoscopic Device Therapies

Some of the unresolved issues include questions about the safety and durability of the device/treatment and lack of consistent improvement in objective measures (esophageal acid exposure) using these devices. Also, the rate of revisional procedures on longer follow-up may be high and needs to be further defined. High-quality data from large randomized controlled trials are needed to compare endoscopic procedures with both sham controls and with the currently accepted treatments for gastroesophageal reflux disease (GERD), i.e., drug therapy and laparoscopic fundoplication. Well-designed trials should use standardized outcome measures to examine whether subjective improvement, such as discontinuation of medication therapy and GERD-HRQL (health-related quality of life) scores, is supported by objective improvement, such as esophageal acid exposure.

The evidence on transesophageal incisionless fundoplication (TIF) in patients who have gastroesophageal reflux disease (GERD) includes 4 small randomized controlled trials (RCTs), registry data, and numerous case series. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. The results from these trials are not conclusive. However, the mean improvement in symptoms scores did not differ between groups. In the other trials, there was improvement on some outcomes. One small RCT compared TIF with laparoscopic Nissen fundoplication, and reported no difference in short-term outcomes. In addition, some outcomes (e.g., medication use) favored the Nissen group though differences were not statistically significant.

The evidence on endoscopic radiofrequency (RF) energy in patients who have GERD includes 4 small RCTs, a nonrandomized comparative study, and observational studies with longer term follow-up. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. The RCTs report improvements in symptoms and quality of life following treatment with RF energy, however, a meta-analysis of these same studies found no significant improvement in outcomes. Nonrandomized studies show maintenance of efficacy at 3 to 10 years, although symptom relief may be lower than after fundoplication, and reoperations greater. Studies comparing Stretta to other minimally invasive procedures for GERD are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

The evidence on esophageal bulking agents in patients who have GERD is limited. Relevant outcomes are symptoms, change in disease status, quality of life, medication use, and treatment-related morbidity. High-quality data from large RCTs are needed to compare bulking procedures with both sham controls and with the currently accepted treatments for GERD (i.e., drug therapy, laparoscopic fundoplication). Well-designed trials should use standardized outcome measures to examine whether subjective improvement (e.g., discontinuation of medication therapy, GERD–Health-Related Quality of Life scores) is supported by objective improvement (e.g., esophageal acid exposure). The evidence is insufficient to determine the effects of the technology on health outcomes.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

43192, 43201, 43210, 43236, 43253, 43257, 43289, 43499

HCPCS Codes

None

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. Mar 2013; 108(3):308-328; quiz 329. PMID 23419381

2. van Pinxteren B, Sigterman KE, Bonis P, et al. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2010 (11):CD002095. PMID 21069670

3. U.S. Food and Drug Administration (FDA). 510(k) Summary: EsophyX. 2016; <https://www.accessdata.fda.gov> (accessed September 6, 2016).

4. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Transesophageal Endoscopic Treatments for Gastroesophageal Reflux Disease. TEC Assessment. 2003; Volume 18: Tab 20.

5. Ip S, Bonis P, Tatsoni A, et al. Comparative Effectiveness of Management Strategies for Gastroesophageal Reflux Disease. Evidence Report/Technology Assessment No. 1. (Prepared by Tufts-New England Medical Center Evidence-based Practice Center). AHRQ Publication No. 06-EHC003-EF. Rockville, MD: Agency for Healthcare Research and Quality. 2005; Available at: <http://effectivehealthcare.ahrq.gov> (accessed September 6, 2016).

6. Ip S, Chung M, Moorthy D, et al. Management strategies for gastroesophageal reflux disease: An update. Comparative effectiveness review No. 29 (Prepared by Tufts Medical Center Evidence-based Practice Center under Contract No. HHSA 290-2007-10055-I.) AHRQ Publication No. 11-EHC049-EF. Rockville, MD: Agency for Healthcare Research and Quality. 2011; Available at: <http://effectivehealthcare.ahrq.gov> (accessed September 6, 2016).

7. Humphries LA, Hernandez JM, Clark W, et al. Causes of dissatisfaction after laparoscopic fundoplication: the impact of new symptoms, recurrent symptoms, and the patient experience. Surg Endosc. May 2013; 27(5):1537-1545. PMID 23508812

8. Hummel K, Richards W. Endoscopic treatment of gastroesophageal reflux disease. Surg Clin North Am. Jun 2015; 95(3):653-667. PMID 25965137

9. Blue Cross Blue Shield Association Center for Clinical Effectiveness. Transoral incisionless fundoplication for gastroesophageal reflux disease. Evidence Street Assessment. 2016; (in press).

10. Hunter JG, Kahrilas PJ, Bell RC, et al. Efficacy of transoral fundoplication vs omeprazole for treatment of regurgitation in a randomized controlled trial. Gastroenterology. Feb 2015; 148(2):324-333 e325. PMID 25448925

11. Hakansson B, Montgomery M, Cadiere GB, et al. Randomised clinical trial: transoral incisionless fundoplication vs. sham intervention to control chronic GERD. Aliment Pharmacol Ther. Dec 2015; 42(11-12):1261-1270. PMID 26463242

12. Witteman BP, Conchillo JM, Rinsma NF, et al. Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease. Am J Gastroenterol. Apr 2015; 110(4):531-542. PMID 25823768

13. Trad KS, Barnes WE, Simoni G, et al. Transoral incisionless fundoplication effective in eliminating GERD symptoms in partial responders to proton pump inhibitor therapy at 6 months: the TEMPO Randomized Clinical Trial. Surg Innov. Feb 2015; 22(1):26-40. PMID 24756976

14. Svoboda P, Kantorova I, Kozumplik L, et al. Our experience with transoral incisionless plication of gastroesophageal reflux disease: NOTES procedure. Hepatogastroenterology. Jul-Aug 2011; 58(109):1208-1213. PMID 21937380

15. Frazzoni M, Conigliaro R, Manta R, et al. Reflux parameters as modified by EsophyX or laparoscopic fundoplication in refractory GERD. Aliment Pharmacol Ther. Jul 2011; 34(1):67-75. PMID 21539587

16. Toomey P, Teta A, Patel K, et al. Transoral incisionless fundoplication: is it as safe and efficacious as a Nissen or Toupet fundoplication? Am Surg. Sep 2014; 80(9):860-867. PMID 25197871

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18. Testoni PA, Vailati C, Testoni S, et al. Transoral incisionless fundoplication (TIF 2.0) with EsophyX for gastroesophageal reflux disease: long-term results and findings affecting outcome. Surg Endosc. May 2012; 26(5):1425-1435. PMID 22170317

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Policy History:

DateReason
4/15/2018 Reviewed. No changes.
7/15/2017 Document updated with literature review. Coverage unchanged.
7/15/2016 Document partially updated with literature review. The following coverage change was made: “Transendoscopic therapy as a treatment for gastroesophageal reflux disease (GERD) maybe considered medically necessary for transesophageal endoscopic gastroplasty also known as endoscopic gastroplication, fundoplication or transoral incisionless fundoplication [TIF] (e.g., StomaphyX™, EsophyX™) when meeting ALL the following criteria:Age 18+; Confirmed GERD by endoscopy, ambulatory PH, or barium swallow testing; Greater than one year of GERD symptoms (reflux symptoms that occur 2 to 3 times per week); History of daily PPI’s for > six months; GERD patients with BMI ≤ 35; No Hiatal hernia >2 cm; No Esophagitis LA (Los Angeles classification system) grade C or D; No Barrett’s esophagus >2 cm; Absence of achalasia and esophageal ulcer; No altered esophageal anatomy that would prevent insertion of a device; Esophageal motility disorder; and Previous history of failed antireflux surgery.
4/1/2016 Document updated with literature review. Coverage criteria regarding a laparoscopically implantable magnetic esophageal ring (LINX™ Reflux Management System) was removed and is now addressed on new medical policy document SUR709.036 Magnetic Esophageal Ring to Treat Gastroesophageal Reflux Disease (GERD). Otherwise coverage unchanged.
4/15/2015 Document updated with literature review. Coverage unchanged.
6/15/2013 Document updated with literature review. The following was added: (1) Durasphere and Gatekeeper Reflux Repair System added as examples of an endoscopic submucosal injection or implantation of a prosthetic or bulking agent. (2) A laparoscopically implantable magnetic esophageal ring (LINX™ Reflux Management System) as a treatment device for GERD is considered experimental, investigational and unproven. Title changed from Transendoscopic Therapies for Gastroesophageal Reflux Disease (GERD).
5/15/2011 Document updated with literature review. Coverage unchanged.
9/15/2009 Revised/updated entire document. No change in experimental, investigational, and unproven coverage position. Additional new trade name (EsophyX™) for performing transesophageal endoscopic gastroplasty or gastroplication added to the coverage section.
1/15/2007 Revised/updated entire document
10/1/2004 Revised/updated entire document
8/1/2002 New medical document

Archived Document(s):

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