The Zephyr Endobronchial Valve has the most clinical evidence of any endoscopic lung volume reduction therapy, supported by four published randomized controlled clinical trials, two more underway, and extensive scientific research into safety and efficacy. Click here to see our key publications.

Two additional randomized controlled clinical trials – the US LIBERATE pivotal trial and TRANSFORM – have completed enrollment.

The evidence is accumulating that this is a powerful treatment for emphysema patients. Dr. med. Dirk-Jan Slebos, PhD – UMC Groningen – The Netherlands
This technology has the biggest evidence base and the greatest clinical use. Dr. Pallav Shah, MD – Royal Brompton & Harefield London – United Kingdom

Summary of randomized published clinical trials

Click on one of the indicated studies and you will be directed immediately to more information on the selected study.

IMPACT STUDY

Endobronchial Valve Therapy in Patients with Homogeneous Emphysema. Results from the IMPACT Study
American Journal of Respiratory and Critical Care Medicine, Vol. 194, No. 9, Nov 01, 2016

Patients with homogeneous emphysema also benefit from therapy with endobronchial valves

This new clinical study demonstrates the benefits of Pulmonx Zephyr Endobronchial Valves in patients with homogeneous emphysema.

The positive results of the IMPACT STUDY, published in the American Journal of Respiratory and Critical Care Medicine online (Sept. 2016), demonstrate that patients with homogeneous emphysema benefit from treatment with the Zephyr Endobronchial Valve (EBV®) from Pulmonx. Patients pre-selected with the Chartis® System and treated with EBV, experienced significant improvements in lung function, exercise capacity and quality of life following therapy.

The IMPACT STUDY is the first prospective, randomized, multi-centre study examining the effectiveness of the Zephyr EBV specifically in patients with homogeneous emphysema. The study enrolled and randomized 93 patients with severe homogeneous emphysema to compare the safety and effectiveness of Zephyr EBV treatment versus medical management. The Chartis System was used to select patients with little or no collateral ventilation, and thus most likely to benefit from treatment whilst advanced imaging technology was used to select a target lobe for treatment.

The three-month results from the IMPACT STUDY showed that patients with homogeneous emphysema and little or no collateral ventilation in the target lobe (assessed using the Chartis System) treated with the Zephyr Endobronchial Valve experienced a 17 percent improvement in FEV1 compared to the control group. EBV-treated patients also experienced improved exercise tolerance, with a 40-meter increase over the control group in the Six Minute Walk Test (6MWD), and improved quality of life, with a 10-point improvement in the St. Georges Respiratory Questionnaire (SGRQ) score over the control group. The results also showed that 97 percent of EBV subjects experienced target lobe volume reduction, indicating effective occlusion of the target lobe following Zephyr EBV placement. These data indicate that EBV therapy can benefit substantially more patients than previously believed.

Click here to see detailed information about the IMPACT STUDY.


STELVIO STUDY

Endobronchial Valves for Emphysema without Interlobar Collateral Ventilation
The New England Journal of Medicine 2015; 373:2325-2335.

Karin Klooster, Jorine E. Hartman, Nick H.T. ten Hacken, Dirk-Jan Slebos, University of Groningen, and Department of Pulmonary Diseases, University Medical Center Groningen, Groningen, The Netherlands

See also
One-Year Follow-Up after Endobronchial Valve Treatment in Patients with Emphysema without Collateral Ventilation Treated in the STELVIO Trial
American Journal of Respiratory and Critical Care Medicine, Vol. 194, No. 9, Nov 01, 2016

The STELVIO STUDY, published in the New England Journal of Medicine, was independently conducted and is the first prospective RCT validating use of Chartis System to pre-select patients with low or no collateral ventilation in the target lobe. Following selection, patients were then randomized to EBV therapy or medical management. The results showed that the EBV group had statistically and clinically greater improvements than the control group in pulmonary function, exercise capacity and quality of life. Patients in the control group were allowed to crossover to EBV therapy at the end of six months. Control patients that crossed over to receive EBV therapy achieved improvements in pulmonary function and exercise capacity that were similar to the original EBV-treated group. In addition, EBV therapy was shown to be effective in patients with both heterogeneous and homogeneous emphysema with low collateral ventilation.

Click here to read about the one-year follow-up.

Table 1: STELVIO STUDY publication overview1
Study title Bronchoscopic Lung Volume Reduction with endobronchial valves using best responder criteria in patients with severe COPD – The STELVIO Trial (Netherlands Trial Register number NTR2876).
Design Single-centre, randomized (1:1 EBV vs standard of care) controlled trial
Purpose STELVIO is a prospective, randomized controlled trial comparing use of endobronchial valves (EBV) to standard medical care in patients with severe emphysema and low collateral ventilation as measured by the Chartis System.
Number of patients enrolled
  • 84 patients consented; 16 patients excluded for positive collateral ventilation or bronchoscopy inaccessibility
  • 68 patients randomized
    • 34 patients to EBV group
    • 34 patients to control group
Results

Primary Outcomes in the Intention to Treat Population

STELVIO clincial study primary outcomes in the intention to treat population
  • EBV patients demonstrated a significant improvement vs. control at 6 months on all three primary endpoints on an ITT basis (p<0.01 for all 3 measures)
    • Mean FEV1 (% predicted): 17.8% higher in EBV group
    • Mean FVC (% predicted): 14.4% higher for EBV group
    • Mean 6MWD: 23.3% higher in EBV group

Significantly Greater Responder Rates for EBV-treated Patients than Standard of Care

STELVIO clinical study significantly greater responder rates for EBV-treated patients than standard of care
  • Clinical benefits for both homogeneous and heterogeneous subgroups
  • Rate of complications was similar between groups except for pneumothorax, which was higher in EBV group. By 6 months, 23 serious adverse events had been reported in the EBV group, as compared with 5 in the control group (P<0.001). One patient in the EBV group died. Serious treatment related adverse events in this group included pneumothorax (18% of patients) and events requiring valve replacement (12%) or removal (15%).
Conclusions Endobronchial valve treatment significantly improved pulmonary function and exercise capacity in patients with severe emphysema characterized by an absence of interlobar collateral ventilation.

BeLieVer-HIFI STUDY

Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi STUDY): a randomised controlled trial
The Lancet. 2015; 386(9998):1066-1073.

See also
Endobronchial valves for patients with heterogeneous emphysema and without interlobar collateral ventilation: open label treatment following the BeLieVeR-HIFi study
Thorax Online First, published on December 20, 2016,

The BeLieVeR-HIFi STUDY published in the Lancet was an independent, randomized, double-blind, sham-controlled study in patients with both heterogeneous emphysema and a target lobe with intact interlobar fissures on CT of the thorax. The study included patients with low collateral ventilation determined by chest CT imaging; Chartis System assessments were also performed to evaluate collateral ventilation, but not used to determine inclusion in the study. Using the most rigorous study design available, a sham procedure as a control, the study exceeded its primary endpoint, with a 20.9% greater average improvement in FEV1 (% predicted) than control. The median improvement vs. control was less pronounced, with 5.9% greater average improvement in FEV1 in treated patients than control, in part due to the inclusion of 7 out of 25 patients in the treatment group who had tested positive for collateral ventilation or had indeterminate Chartis results..

Table 2: BeLieVeR-HIFi STUDY publication overview2,3
Study title Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and interlobar fissures (the BeLieVeR-HIFi STUDY): a randomised controlled trial (ISRCTN04761234)
Design Single centre, randomized (1:1), parallel group, double-blind sham bronchoscopy controlled trial
Purpose BeLieVeR-HIFi is a prospective, double-blind, randomized, sham-controlled trial comparing use of endobronchial valve for severe emphysema patients to a sham bronchoscopy procedure.
Number of patients enrolled
  • 50 patients selected based on visual CT assessment of fissure integrity and randomized
    • 25 patients to BLVR group
    • 25 patients to control group (sham valve placement)
Results
  • EBV patients demonstrated significant improvements in FEV1 and exercise capacity vs. control at 3 months.
  • Between group differences at 3 months:
    • Mean FEV1 (% predicted): 20.9%
    • Median FEV1 (% predicted): 5.9% (p=0.0326)
    • Mean 6MWD: 33m
    • Median 6MWD: 22m (p=0.0119)
  • The response in the BLVR group was heavily skewed so non-parametric tests were used for analysis (Mann-Whitney). Thus the results were expressed with the median.
  • Pneumothorax occurred in two treated patients (8%) and in one control patient (4%). There were two deaths in the BLVR group. One in the BLVR group occurred as a complication of valve removal, which was difficult. There was one control patient who was unable to attend for follow-up assessment because of a prolonged pneumothorax
Conclusions This study demonstrates that, in patients with heterogeneous emphysema and intact interlobar fissures, endobronchial valve placement is effective in improving lung function to a clinically significant extent. However, this is not without risks, including, in particular, the possibility of pneumothorax.

VENT STUDY

A Randomized Study of Endobronchial Valves for Advanced Emphysema
The New England Journal of Medicine 2010; 363:1233-1244.

Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort
European Respiratory Journal 2012; 39: 1334-1342.

The VENT study is a multicenter, prospective, randomized, controlled trial conducted to evaluate safety and effectiveness of the unilateral treatment of emphysema by endobronchial valves (EBV). It was conducted in the USA and Europe from 2004 to 2009 and sponsored by Emphasys

Note: this study was conducted prior to the availability of devices to measure the collateral ventilation (CV) e.g. Chartis system. Collateral ventilation was not used to select patients for inclusion in the study, and investigators frequently did not completely occlude the targeted lobe for treatment. Only 68 of 214 treated patients had complete fissures (and thereby a low likelihood of collateral ventilation); of these 68, only 37 had complete occlusion of the target lobe with valves. Thus of the 214 treated patients, only 17% received treatment consistent with current clinical practice of selecting lobes without collateral ventilation and completing occluding them. The result was to decrease the average effect of the treatment, as was shown later in post hoc analysis*.

Data were analyzed and reported for two cohorts (US VENT cohort (321 patients) and EURO VENT cohort (171 patients).

A study publication overview is provided in Table 3

Table 3: VENT STUDY publication overview4,5
Study title Endobronchial Valve for Emphysema Palliation Trial (VENT) (NCT00129584)
Design Multicenter, randomized (2:1), controlled trial
Purpose Compare efficacy and safety of endobronchial valve (EBV) therapy in patients with heterogeneous emphysema versus standard medical care (control)
Number of patients enrolled
  • 492 patients randomized (US:321, EU: 171)
    • 331 patients to EBV group (US: 220, EU :111)
    • 161 patients to control group (US: 101, EU: 60)
Published results
  • EBV patients demonstrated a significant improvement vs. control at 6 and 12 months in FEV1, exercise capacity and quality of life
  • FEV1 – All patients:
    • 6 mo: US: +6.8% (p=0.005), EU: +6.5% (p=0.067)
    • 12 mo: US: + 7.7% (p=0.003), EU: +8% (p=0.0499)
  • FEV1 – Selected patients with complete fissure:
    • 6 mo: US: +16.2% (p<0.001), EU: +14% (p=.02)
    • 12 mo: US: +17.9% (p<0.001), EU: +17% (p=0.04)
  • Exercise ability – Mean increase in exercise ability documented by cycle ergometry or 6MWT distance in EBV group vs control:
    • US cohort:
      +19.1 m (p=0.02) at 6 months
      11.7 m (p=0.17) at 12 months
    • EU cohort:
      +5 W (p=0.04) at 6 months
      +6 W at 12 months (p=0.03)
  • Quality of life changes – Mean decrease SGRQ score in EBV vs control group*:
    • US: -3.4 (p=0.4) at 6 months
      EU: -5.3 (p=0.047) at 6 months
* 12 month SGRQ score not reported in publication
Post hoc analysis
  • VENT Clinical data were recently re-analyzed using most recent tools available to detect fissure completeness, lobar occlusion and target lobe volume reduction7
  • Among the 331 treated patients, 122 were found to qualify for fissure completeness, lobar occlusion and target lobe volume reduction greater than 350 ml.
  • At the 6 mo follow-up, patients exhibited the following improvement in lung function, exercise capacity (6mWT) and quality of life (SGRQ).
  • FEV1:+24.7%
  • 6mWTd: +28 m
  • SGRQ: -8.4 points
  • This subgroup of highly selected patients, analyzed retrospectively, support the results obtained from the prospective randomized trials conducted afterwards i.e STELVIO, BeLieVeR-HIFi and IMPACT.
Conclusions Both publications conclude that unilateral lobar volume reduction using endobronchial valve treatment result in modest improvements in lung function, exercise tolerance, and symptoms. Superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion.
  1. Valipour A, et al. Am J Respir Crit Care Med. 2016.
  2. Klooster K, ten-Hacken Nick HT, Hartman JE, Kerstjens Huib AM, van Rikxoort EM, and Slebos DJ. Endobronchial Valves for Emphysema without Interlobar Collateral Ventilation. N Engl J Med. 2015; 373:2325-2335.
  3. Davey C, Zoumot Z, Jordan S, McNulty WH, Carr DH, Hind MD, Hansell DM, Rubens MB, Banya W, Polkey MI, Shah PL, and Hopkinson NS. 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. 2015; 386(9998):1066-1073.
  4. Zoumot Z, Davey C, Jordan S, McNulty WH, Carr DH, Hind MD, et al. A randomised controlled study of Bronchoscopic Lung Volume Reduction with endobronchial valves for patients with Heterogeneous emphysema and Intact interlobar Fissures: the BeLieVeR-HIFi study. Efficacy Mech Eval 2015;2(5).
  5. Herth FJF, Noppen M, Valipour A, Leroy S, Vergnon J-M, Ficker JH, Egan JJ, Gasperini S, Agusti C, Holmes-Higgins D, Ernst A, on behalf of the VENT STUDY Group. Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort. Eur Respir J 2012; 39: 1334-1342.
  6. Sciurba S. F, Ernst A, Herth FJF, Strange C, Criner GJ, Marquette CH, Kovitz KL, Chiacchierini RP, Goldin J, and McLennan G, for the VENT STUDY Research Group. A Randomized study of Endobronchial Valves for Advanced Emphysema. N Engl J Med 2010; 363:1233-1244.
  7. Internal analysis
  • *On file at Pulmonx
Clinical summary (download)