Medical Policies - Surgery


Endobronchial Valves

Number:SUR706.015

Effective Date:10-15-2017

Coverage:

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Endobronchial valves are considered experimental, investigational and/or unproven for all indications, including but not limited to treatment of patients with the following:

Prolonged air leaks, OR

Chronic obstructive pulmonary disease (COPD) or emphysema.

Description:

Endobronchial valves are synthetic devices that are deployed with bronchoscopy into ventilatory airways of the lung for the purpose of controlling airflow. They have been investigated for use in patients who have prolonged broncho-pleural air leaks, as well as an alternative to lung volume reduction surgery (LVRS) in patients with lobar hyperinflation from severe emphysema.

Air Leaks

Proper lung functioning depends on the separation between the air-containing parts of the lung and the small vacuum-containing space around the lung called the pleural space. When air leaks into the pleural space, the lung is unable to inflate, resulting in hypoventilation and hypoxemia; this condition is known as a pneumothorax. A pneumothorax can result from trauma, high airway pressures induced during mechanical ventilation, lung surgery, and rupture of lung blebs or bullae, which may be congenital or a result from chronic obstructive pulmonary disease (COPD).

Treatment

Although an air leak from the lung into the pleural space may seal spontaneously, it often requires intervention. Techniques currently employed to close air leaks include the following:

Inserting a chest tube (tube thoracostomy) and employing a water seal or one-way valve to evacuate air collected in the pleural space and prevent it from reaccumulating;

Lowering airway pressures by adjusting the mechanical ventilator;

Using autologous blood patches; and

Performing a thoracotomy with mechanical or chemical pleurodesis.

A bronchial valve is a device that permits one-way air movement. During inhalation, the valve is closed, preventing air flow into the diseased area of the lung. The valve opens during exhalation to allow air to escape from the diseased area of the lung. When used to treat persistent air leak from the lung into the pleural space, the bronchial valve theoretically permits less air flow across the diseased portion of the lung during inhalation, aiding in air leak closure. The valve may be placed, and subsequently removed, by bronchoscopy.

Bronchial valves have also been investigated for use in severe emphysematous COPD. In emphysematous COPD, peripheral lung tissue may form bullae. These diseased portions of the lung ventilate poorly, cause air trapping, and hyperinflate, compressing relatively normal lung tissue. They also may rupture, causing a pneumothorax. Use of a bronchial valve is thought to prevent hyperinflation of these bullae.

Use of bronchial valves in COPD is based on the improvement observed in patients who have undergone lung volume reduction surgery. Lung volume reduction surgery involves excision of peripheral emphysematous lung tissue, generally from the upper lobes. The precise mechanism of clinical improvement for patients undergoing lung volume reduction has not been firmly established. However, it is believed that elastic recoil and diaphragmatic function are improved by reducing the volume of the diseased lung. The procedure is designed to relieve dyspnea and improve functional lung capacity and quality of life; it is not curative.

Bronchial valves have been investigated as a nonsurgical alternative to lung volume reduction surgery.

Regulatory Status

In October 2008, the Spiration® IBV System (Spiration, Redmond, WA) was approved by the U.S. Food and Drug Administration (FDA) through the humanitarian device exemption process for use in controlling prolonged air leaks of the lung or significant air leaks that are likely to become prolonged air leaks following lobectomy, segmentectomy, or lung volume reduction surgery. An air leak present on postoperative day 7 is considered prolonged unless present only during forced exhalation or cough. An air leak present on day 5 should be considered for treatment if it is: [1] continuous, [2] present during the normal inhalation phase of inspiration, or [3] present on normal expiration and accompanied by subcutaneous emphysema or respiratory compromise. Use of the intrabronchial Valve System is limited to 6 weeks per prolonged air leak. Use of the Spiration® Intrabronchial Valve for emphysema is considered off-label. FDA product code: OAZ.

In December 2008, the Zephyr® Endobronchial Valve (formerly by Emphasys Medical, now Pulmonx, Redwood City, CA) was considered by an FDA panel for use as a permanent implant intended to improve forced air expiratory volume in 1 second and 6-minute walk test distance in patients with severe, heterogeneous emphysema who have received optimal medical management. The panel declined to recommend the device for FDA approval. As of May 2017, the Zephyr® Endobronchial Valve has not been approved by the FDA.

Rationale:

This medical policy was originally created in January 2011 and has been updated regularly with searches of the MEDLINE database. The most recent literature review was performed through July 2017. A summary of the key literature follows.

Treatment of air leaks

No randomized controlled trials (RCTs) or comparative observational studies were identified. Only case series and case report data are available. The largest case series, published in 2009, reported on 40 patients treated at 17 sites in the United States and Europe; 6 of the patients had been included in previously published case reports. (1) Zephyr (Emphasys, now Pulmonx) endobronchial valves were used. Data were abstracted retrospectively from medical records. No specific eligibility criteria were reported, and patients did not need to demonstrate that they were refractory to other treatments. All patients in the series had prolonged pulmonary air leak (mean duration, 119 days; median, 20 days). Twenty-five patients had continuous air leaks, 14 had expiratory air leaks, and one was unidentified. The most common comorbidities were cancer and chronic obstructive pulmonary disease (COPD). Prior to the procedure, 39 of the 40 patients had at least 1 chest tube. Five patients had other treatments e.g., blood patch before valve placement. The mean number of valves placed per patient was 2.9 (SD=1.9) overall. After valve placement, 19 patients (47.5%) had complete resolution of acute air leak, 18 (45%) had a reduction in air leak, 2 (5%) had no change, and data were not available for 1 patient. The mean time from valve placement to chest tube removal was 21 days, and the median time was 7.5 days (data from 2 patients were not available). Eight patients had the valves removed after the air leak ceased; in 32 patients, the clinician chose to leave the valves in place. Six patients experienced adverse effects related to valve placement including valve expectoration, moderate oxygen desaturation, initial malpositioning of a valve, pneumonia and Staphylococcus aureus colonization. The length of follow-up was highly variable, ranging from 5 to 1109 days. At last follow-up, 16 patients were reported to have died; none of the deaths were attributed to the valve or the valve implantation procedure.

The next largest case series published to date was 2013 study by Firlinger et al. in Austria. (2) The study included 16 patents with persistent continuous air leak i.e., having an intrathoracic chest tube for more than 7 days, despite conservative and/or surgical therapy. Endobronchial valves were placed in 13 of 16 patients; the source of the air leak could not be identified in the other 3 individuals. The Food and Drug Administration (FDA) ?approved Spiration IBV valves were used in 9 patients and Zephyr valves were used in the other 3 patients. Ten of 13 (77%) patients were considered responders, defined as patients in whom successful chest tube removal occurred without the need for further intervention. Spiration IBV valves were used in 6 of 10 responders and all 3 nonresponders.

In addition, a 2011 case series reported on 9 patients with pulmonary air leaks evaluated for treatment with Spiration IBV valves. (3) Target airways could not be identified in 2 patients, and valves were placed in 7 patients. One of the 7 had 2 procedures due to development of an additional air leak after the first one was treated and resolved. The median duration of air leaks in the 7 patients before valve placement was 4 weeks (range, 2 weeks to 5 months). Complete air leak cessation occurred in 6 of 8 procedures after a mean duration of 5.2 days. The other 2 procedures resulted in reduction of air leak. There were no operative or postoperative complications attributed to the bronchial valves. The valves were removed in 5 of the 7 patients at a mean of 37 days after placement (range, 14-55 days). Valves were not removed in one patient who entered hospice care and in the patient who underwent 2 procedures because the patient declined removal.

Section Summary: Treatment of Air Leaks

The only available data on endobronchial valves for treating persistent air leaks are uncontrolled trials with small numbers of heterogenous patients. Data on the FDA-approved endobronchial valve device are particularly limited; Spiration valves were successfully placed in 7 patients in 1 case series and 9 patients in another. This evidence is not adequate to determine the impact of this technology on the net health outcome, nor does it provide any evidence on comparisons with alternatives.

Treatment of Severe or Advanced Emphysema

A 2017 Cochrane review by van Agteren et al. included 5 trials with a total of 703 patients who were treated with either the Zephyr® EBV or medical management for chronic obstructive pulmonary disease (4) Trials included were Valve for Emphysema Palliation Trial (VENT) (U.S. and E.U.), BeLieVeR-HIFi, IMPACT, and STELVIO. The VENT and BeLieVeR-HIFi are described in greater detail below. The meta-analysis found that Zephyr® valves led to significant improvements in lung function (including the forced air expiratory volume in 1 second (FEV1)), quality of life (including St George’s Respiratory Questionnaire (SGRQ)) and exercise capacity (6-minute walk test (6MWT, Table 1). The SGRQ scores range from 0 to 100, with higher scores indicating worse quality of life. There were no significant differences in mortality between the two groups, but adverse events were more common in the EBV group.

The evidence on the Spiration® IBV included 2 trials (Ninane 2012, IBV Valve Trial). (5) One trial found a benefit for lung function (including FEV1) and exercise capacity (6MWT) while the other did not. There were no significant differences in quality of life (including SGRQ scores) or mortality rates, but adverse events were more frequent in the IBV group.

Table 1: Results of van Agteren et al. Meta-Analysis

Outcomes

Zephyr® EBV

95% CI

p

Spiration® IBV

95% CI

p

FEV1 SMD

0.48

0.32 to 0.64

<0.001

-2.15

-3.47 to -0.83

SGRQ MD

-7.29 units

-11.2 to -3.45

<0.001

2.64

-0.28 to 5.56

NS

6MWT SMD

38.12

8.68 to 67.56

0.011

-19.54

-37.11 to -1.98

0.029

Mortality OR

1.07

0.47 to 2.43

NS

4.95

0.85 to 28.94

NS

Adverse events OR

5.85

2.16 to 15.84

<0.001

3.41

1.48 to 7.84

0.004

CI: confidence interval; EBV: Endobronchial Valve; FEV: Forced air expiratory volume in 1 second; IBV: intrabronchial valve; MD: mean difference; OR: odds ratio; SGRQ: St. George’s Respiratory Questionnaire; 6MWT: 6-minute walk test; SMD: standardized mean difference

Randomized controlled trials

Endobronchial Valve for Emphysema Palliation Trial (VENT)

VENT was randomized but not blinded. Primary results were published by Sciurba et al. (U.S. cohort) (6) and Herth et al. (European cohort). (7) Key eligibility criteria for participation were diagnosis of heterogeneous emphysema, FEV1 of 15% to 45% of the predicted value, total lung capacity of more than 100% of predicted value, residual volume of more than 150% of predicted value, and post rehabilitation 6MWT distance of at least 140 meters. Before randomization, all patients received 6 to 8 weeks of pulmonary rehabilitation and medical management optimized at the discretion of the treating physician, using guidelines from the Global Initiative for Chronic Obstructive Lung Disease. Patients who remained eligible for the trial after undergoing the preliminary treatment program were randomized to receive therapy using the Zephyr endobronchial valve or to standard care. Patients were followed for 12 months, and primary outcomes were reported after 6 months. The primary effectiveness outcomes were percent change from baseline to 6 months in the FEV1 and 6MWT distance. Primary results from the 31 U.S. sites were reported in 2010; results from the 23 sites in Europe were reported in 2012. Pooled 6-month outcomes from both cohorts were reported in 2013. A limitation of the trial design was its lack of blinding, which could have affected performance on the primary efficacy outcomes (e.g., it might have affected clinicians’ coaching of patients and/or the degree of effort exerted by patients).

U.S. Cohort findings:

As reported by Sciurba et al., 321 patients in the U.S. were randomly assigned on a 2:1 basis to receive Zephyr endobronchial valves (n=220) or standard medical care (n=101). (6) The mean number of valves placed in the endobronchial valve group was 3.8 per patient (range, 1-9). The primary effectiveness outcomes were percent change from baseline to 6 months in the FEV1 and distance on the 6-minute walk test. A total of 42 of 220 (19.1%) in the endobronchial valve group and 28 of 101 (27.7%) in the control group had missing data for the primary efficacy outcomes. Of the 70 patients with missing data, 6 had died, 4 were too ill to participate, and 60 dropped out or did not have follow-up within the specified time window. The data analysis was intention-to-treat and missing data were imputed. Primary outcome data at 6 months were as follows:

Table 2. Primary Outcomes Data at 6 Months in the U.S. Cohort of VENT (6)

Outcome

Endobronchial valve Group (n=220)

Control Group (n=101)

Between-Group Difference

FEV1,

Mean absolute percentage change from baseline

4.3 (1.4 to 7.2)

-2.5 (-5.4 to 0.4)

6.8 (2.1 to 11.5)

p=0.005

Distance on 6-minute walk test,

Medial change from baseline

9.3 (-0.5 to 19.1)

-10.7 (-29.6 to 8.1)

19.1 (1.3 to 36.8) p=0.02

Median absolute percentage change from baseline

2.5 (-1.1 to 6.1)

-3.2 (-8.9 to 2.4)

5.8 (0.5 to 11.2)

p=0.04

Among the secondary outcomes reported at the 6-month follow-up, quality of life was measured using the St. George’s Respiratory Questionnaire (SGRQ), which ranges from 0 to 100, with a higher score indicating a worse quality of life. At 6 months, the SGRQ score decreased -2.8 points (95% confidence interval [CI], -4.7 to -1.0) in the endobronchial valve group and increased 0.6 points (95% CI, -1.8 to 3.0) in the control group. The between-group difference was -3.4 (95% CI, -6.7 to 0.2), which was statistically significant (p=0.04) but was less than the 4 points generally considered to represent a clinically meaningful difference. (6) According to body plethysmography, the mean change in total lung volume at 6 months was -1.2 (SD=10.6) in the endobronchial valve group and -0.4% (SD=13) in the control group; this difference was not statistically significant (p=0.41). Similarly, changes between groups in residual volume and inspiratory capacity were not statistically significant.

The primary safety variable was a composite measure consisting of 6 major complications (death, empyema, massive hemoptysis, pneumonia distal to valves, pneumothorax or air leak of more than 7 days’ duration or ventilator-dependent respiratory failure for more than 24 hours). The rate by 6 months was 6.1% in the endobronchial group and 1.2% in the control group. The between-group difference was 4.9% (95% CI, 1.0 to 8.8), which was not statistically different (p=0.08) and fell within the prespecified safety criteria. The adverse events to 6 months included 6 deaths (2.8%) in the endobronchial valve group and no deaths in the control group (p=0.19). Between 3 and 12 months, 25 of 214 (11.7%) patients in the endobronchial valve group followed over this time experienced COPD exacerbations; 22 of these events resulted in hospitalization. Over the same time period, 8 of 87 (9.2%) patients in the control group had COPD exacerbations, all of which resulted in hospitalization. The difference in number of exacerbations was not statistically significant. For hemoptysis (other than massive) between 3 and 12 months, there were 13 (6.1%) cases in the endobronchial valve group and none in the control group (p=0.02). Among the 214 patients who received valves and were followed to 12 months, there were 6 cases (2.8%) of valve expectoration, aspiration, or migration and 9 cases (4.2%) of bronchial granulation tissue. Valves were removed in 31 (14%) patients after 1 to 377 days; removal was based on investigators’ discretion; there was no specific protocol.

European Cohort Findings:

Herth et al. reported on 171 patients in the European cohort of the VENT; 111 patients were randomized to the endobronchial valve group and 60 patients to the standard care group. (7) During the course of the study, 10 patients died and 4 patients withdrew from the study. The number of patients who were lost to follow-up or missed a visit was 12 at 6 months and 21 at 12 months. A total of 154 of 171 (90%) patients completed the 6-month follow-up and 136 of 171 (80%) completed the 12-month follow-up. Primary outcome data at 6 months in the European cohort were as follows (outcome reporting was slightly different than it was in the U.S. cohort):

Table 3. Primary Outcomes Data at 6 Months in the European Cohort of VENT (7)

Outcome

Endobronchial valve Group (n=220)

Control Group (n=101)

Between-Group Difference

FEV1,

Mean absolute percentage change from baseline

7 (20)

0.5 (19)

0.067

Distance on 6-minute walk test,

Medial change from baseline

15 (91)

10 (78)

0.070

Median absolute percentage change from baseline

2 (14)

-3 (10)

0.04

At 12 months, mean (SD) change in FEV1 was 6 [26] in the endobronchial valve group and -2 [20] in the control group, p=0.0499. The mean (SD) change in cycle ergometry workload was 1 watt [13] in the endobronchial valve group and -5 watts [12] in the control group, p=0.03. Data on the 6-minute walk test at 12 months were not reported. Twenty percent of randomized patients did not provide data at 12 months.

Findings on the composite safety variable, reported for the U.S. cohort, were not reported for the European cohort. Herth et al. reported that serious complications and the rate of COPD exacerbations in the European cohort did not differ significantly between groups, and there were no reported cases of emphysema or massive hemoptysis. Five cases of pneumothorax requiring hospitalization for longer than 7 days were reported in the endobronchial valve group. There were 10 deaths, 6 in the endobronchial valve group and 4 in the control group; none were considered to be related to study procedures. Over the 12-month follow-up period, there were 13 cases of valve expectoration, aspiration or migration; this represented 12% of the 111 patients in the endobronchial valve group. Eight of 13 events occurred in the first 90 days after valve placement.

Pooled Cohort Data:

Data from 416 of the 492 (84.6%) patients randomized in both cohorts who received follow-up computed tomography scans at 6 months were reported by Valipour et al. in 2013. (9) Of the 416 patients, 284 were in the endobronchial valve group and 132 were in the control group. The authors reported on several outcomes using an intention-to-treat approach; these outcomes were not originally listed as either primary or secondary outcome measures in the Sciurba et al. report (6). At 6 months, the mean target lobar volume reduction was significantly higher in patients receiving endobronchial valve therapy than in control patents (-242 mL vs 0.5 mL, p<0.001). Moreover, 42% of patients in the endobronchial valve group and 24.7% of controls had improvement of at least 1 point in the BODE index at 6 months (p<0.001). (The BODE index combines several variables, including the FEV1 and the distance on the 6-minute walk test. A higher score on the BODE index has been found to correlate with an increased risk of death from COPD). Valipour et al. did not discuss missing data on the FEV1 or 6-minute walk test measures at 6 months.

Bronchoscopic Lung Volume Reduction with Endobronchial Valves Reduces Dynamic

Hyperinflation Trial

Government-funded, the BeLieVeR-HIFi trial evaluated the Zephyr EBV in a double-blind sham-controlled trial of 50 patients with heterogeneous emphysema and intact interlobar fissures. (10) The patient population was based on the subgroup analysis of VENT, which showed greater efficacy of bronchial valves in patients with these characteristics. Included were patients with a FEV1 of less than 50% of predicted, significant hyperinflation, a restricted exercise capacity, and substantial breathlessness. The minimum clinically important differences were prespecified as a 15% increase for FEV1 (primary outcome), a 350- mL reduction in the residual volume, a 4-point decrease in SGRQ score, a 2-point decrease in the COPD Assessment Test (CAT) score, a 105-second increase in endurance cycle time, and an 26-meter increase in 6MWT distance. Patients were randomized 1:1 to bronchoscopy plus valve placement or to bronchoscopy with sham valve placement. Valve placement led to statistically significant improvements in response rates for some outcomes compared with the sham procedure. Statistically significant differences in response rates were observed for FEV1, 6MWT distance, and endurance cycle time, but not residual volume, SGRQ score, or CAT score (see Table 4). Two patients in the bronchoscopy plus valve placement group died within 90 days of the procedure, 2 had pneumothoraces, and 4 patients expectorated a valve before 3 months.

Table 4. Three-Month Response Rates for the BeLieVeR-HIFi Trial (10)

Outcomes

Endobronchial Valve Group (n=25), %

Control Group (n=25), %

P Value for Between-Group Difference

Forced air expiratory volume in 1 second

39

4

0.004

Residual volume

48

29

0.24

Six-minute walk time distance

52

17

0.012

Endurance cycle time

43

8

0.008

SGRQ score

48

46

1.0

CAT score

57

29

0.08

CAT: COPD Assessment Test; SGRQ: St. George’s Respiratory Questionnaire.

The IBV Valve Trial

Published by Wood et al. (2014), the IBV Valve Trial was randomized and double-blind. (11) Key eligibility criteria for participation were age (40-74 years), diagnosis of emphysema with severe dyspnea, and no more than 2 hospitalizations for COPD exacerbation or respiratory infection within the past year. Medical management was optimized before trial participation, and patients eligible for lung volume reduction surgery or lung transplant received surgical counseling. All trial participants underwent anesthesia for bronchoscopy and were then randomized on a 1:1 basis to active treatment (placement of IBV) or to sham treatment (no valve placement). Patients were assessed at 1, 3, and 6 months. The primary effectiveness outcome was a composite measure including change in disease-related quality of life, as defined by the SGRQ score. A reduction in SGRQ total score of at least 4 points from baseline was considered a clinically meaningful improvement. The composite measure also included a change in lobar lung volume measured by quantitative computed tomography. The computed tomography threshold was at least a 10% increase in non-upper-lob volume and any decrease in upper-lobe volume. The primary safety measure was the difference between groups in the number of serious adverse events.

The trial used an adaptive design with Bayesian statistical methodology. Subject recruitment was planned to stop if prespecified criteria involving Bayesian predictive probabilities were met; potential sample sizes ranged from 200 to 500 patients. In actuality, 277 patients were randomized at 36 sites, 142 to the treatment group and 135 to the control group. A total of 121 (85%) patients in the treatment group and 134 (99%) in the control group completed the 6-month follow-up visit.

As shown in Table 5, 5% of patients in the treatment group and 0.7% in the control group were considered responders. Using Bayesian analysis, the posterior probability superiority in the treatment group was 97%, which exceeded the prespecified success of 95%. However, despite this statistical finding, the authors found that the response rate in the treatment group so low that it could not be considered a clinically meaningful finding.

Table 5. Composite Effectiveness Measure and Individual Components (11)

Outcomes

Treatment Group (n=142)

Control Group (n=135)

Difference (Treatment – Control), 95% BCrI

Composite measure

No. of responders (%)

6/121 (5.0%)

1/134 (0.7%)

0.048% to 9.212%a

SGRQ score

No. of responders (≥ -4 points) (%)

39/121 (32.3%)

53/133 (39.8%)

-19.9% to 4.2%

Computed tomography volume, mL

Mean upper-lobe change (SD)

Mean non-upper-lobe change (SD)

-224 (299) 214 (384)

-17 (204) -27 (292)

-272 to -14a 155 to 326a

BCrI: Bayesian credible interval; SGRQ: St. George’s Respiratory Questionnaire.

a Statistically significant.

Regarding safety, significantly more patients had a serious adverse event in the treatment group (n=20 [14%]) than the control group (n=5 [3.7%]). The most frequent event was COPD exacerbations (7 in the treatment group, 4 in the control group). Six patients in the treatment group and 1 in the control group died; no deaths were considered device-related. A pneumothorax occurred in 3 (2.1%) patients, all in the treatment group.

Section Summary: Treatment of Severe or Advanced Emphysema

For patients with severe or advanced emphysema, 7 published RCTs and a systematic review of these trials have provided insufficient evidence that the technology improves the net health outcome. VENT was limited by a lack of blinding and a large amount of missing data. For pooled trial data from the U.S. and European cohorts of VENT, the magnitudes of the primary outcomes that were statistically significant represented uncertain clinical significance. Results from the sham-controlled BeLieVeR-HIFi trial were mixed, with significant differences in response rates for FEV1, 6MWT distance, and endurance cycle time, but not for residual volume, SGRQ score, or CAT score. Authors of the sham-controlled IBV Valve Trial concluded study findings did not indicate a clinically meaningful benefit of the Spiration IBV for patients with severe emphysema. Additionally, patients who received either bronchial valve device experienced numerous adverse events.

Summary of Evidence

For individuals who have pulmonary air leaks who receive bronchial valves, the evidence includes case series. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, and treatment-related morbidity. The only available data on bronchial valves for treating persistent air leaks are uncontrolled trials with small numbers of heterogeneous patients. Data on the Spiration IBV device (the only device approved by the U.S. Food and Drug Administration) are particularly limited. These valves were successfully placed in 40 patients in a multicenter case series and other series. These case series do not provide any comparative evidence with alternatives. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have severe or advanced emphysema who receive bronchial valves, the evidence includes 7 randomized controlled trials and a systematic review of these trials. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life, and treatment-related morbidity. Of the 7 randomized controlled trials, 5 did not use a U.S. Food and Drug Administration approved valve. For the U.S. Food and Drug Administration approved Spiration IBV, there was no improvement in quality of life or exercise capacity in the combined results. Although some outcomes of the larger trials were statistically significant for bronchial valve treatment, the magnitude of the difference was generally of uncertain clinical significance. Moreover, the numerous adverse events experienced by patients who received bronchial valves in these trials raise concerns about treatment safety. Overall, it is not possible to determine whether there is a clinically meaningful benefit. The evidence is insufficient to determine the effects of the technology on health outcomes.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 6.

Table 6. Summary of Key Trials

NCT No.

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT01812447a

A Prospective, Randomized, Controlled Multicenter Clinical Study to Evaluate the Safety and Effectiveness of the Spiration® Valve System for the Single Lobe Treatment of Severe Emphysema (EMPROVE)

271

Nov 2017

NCT02382614a

Safety and Effectiveness of the Spiration Valve System (SVS) in Air Leaks (VAST)

200

Dec 2017

NCT02022683a

A Multi-center, Prospective, Randomized, Controlled Trial of Endobronchial Valve Therapy vs. Standard of Care in Heterogeneous Emphysema (TRANSFORM)

78

Feb 2018

NCT01796392a

Lung Function Improvement After Bronchoscopic Lung Volume Reduction With Pulmonx Endobronchial Valves Used in Treatment of Emphysema (LIBERATE)

183

Sept 2021

Unpublished

NCT01989182a

The Spiration Valve System for the Treatment of Severe Emphysema (SVS)

101

Mar 2017 (completed)

NCT: national clinical trial.

a Denotes industry-sponsored or cosponsored trial.

Practice Guidelines, and Position Statements

In 2011, the British Thoracic Society published guidelines on advanced diagnostic and therapeutic flexible bronchoscopy in adults. (12) The guidelines stated that sufficient evidence has not yet been demonstrated to recommend the routine use of endobronchial valves for treatment of emphysema.

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

31647, 31648, 31649, 31651

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. Travaline JM, McKenna RJ, Jr., De Giacomo T, et al. Treatment of persistent pulmonary air leaks using endobronchial valves. Chest. Aug 2009; 136(2):355-360. PMID 19349382

2. Firlinger I, Stubenberger E, Muller MR, et al. Endoscopic one-way valve implantation in patients with prolonged air leak and the use of digital air leak monitoring. Ann Thorac Surg. Apr 2013; 95(4):1243-1249. PMID 23434254

3. Gillespie CT, Sterman DH, Cerfolio RJ, et al. Endobronchial valve treatment for prolonged air leaks of the lung: a case series. Ann Thorac Surg. Jan 2011; 91(1):270-273. PMID 21172529

4. Van Agteren JE, Hnin K, Grosser D, et al. Bronchoscopic lung volume reduction procedures for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. Feb 23 2017; 2: CD012158. PMID 28230230

5. Ninane V, Geltner C, Bezzi M, et al. Multicentre European study for the treatment of advanced emphysema with bronchial valves. Eur Respir J. Jun 2012; 39(6):1319-1325. PMID 22654006

6. Sciurba FC, Ernst A, Herth FJ, et al. A randomized study of endobronchial valves for advanced emphysema. N Engl J Med. Sep 23 2010; 363(13):1233-1244. PMID 20860505

7. Herth FJ, Noppen M, Valipour A, et al. Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort. Eur Respir J. Jun 2012; 39(6):1334-1342. PMID 22282552

8. Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Respir Med. Sep 1991; 85 Suppl B (Suppl B):25-31; discussion 33-27. PMID 1759018

9. Valipour A, Herth FJ, Burghuber OC, et al. Target lobe volume reduction and COPD outcome measures after endobronchial valve therapy. Eur Respir J. Feb 2014; 43(2):387-396. PMID 23845721

10. Davey C, Zoumot Z, Jordan S, et al. Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi study): a randomised controlled trial. Lancet. Sep 12 2015; 386(9998):1066-1073. PMID 26116485

11. Wood DE, Nader DA, Springmeyer SC, et al. The IBV Valve trial: a multicenter, randomized, double-blind trial of endobronchial therapy for severe emphysema. J Bronchology Interv Pulmonol. Oct 2014; 21(4):288-297. PMID 25321447

12. Du Rand IA, Barber PV, Goldring J, et al. Summary of the British Thoracic Society guidelines for advanced diagnostic and therapeutic flexible bronchoscopy in adults. Thorax. Nov 2011; 66(11):1014-1015. PMID 22003155

13. Endobronchial Valves. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference manual (2017 June) Surgery 7.01.128.

Policy History:

Date Reason
10/15/2017 Document updated with literature review. Coverage unchanged.
10/1/2016 Reviewed. No changes.
2/1/2015 Document updated with literature review. Coverage unchanged; however all other sections were completely revised and updated.
1/1/2011 New medical document. Endobronchial valves are considered experimental, investigational and unproven for all indications, including but not limited to treatment of patients with prolonged air leaks, COPD or emphysema.

Archived Document(s):

Title:Effective Date:End Date:
Bronchial Valves01-01-202204-14-2022
Bronchial Valves11-01-202012-31-2021
Bronchial Valves02-15-202010-31-2020
Endobronchial Valves10-15-201702-14-2020
Endobronchial Valves10-01-201610-14-2017
Endobronchial Valves02-01-201509-30-2016
Endobronchial Valves01-01-201101-31-2015
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