Elsevier

The Lancet

Volume 378, Issue 9795, 10–16 September 2011, Pages 997-1005
The Lancet

Articles
Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial

https://doi.org/10.1016/S0140-6736(11)61050-7Get rights and content

Summary

Background

Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema.

Methods

We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of ≥0·65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0·965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612.

Findings

All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0·749, below the Bayesian success threshold of 0·965). The 6-month composite primary safety endpoint was 14·4% (30 of 208) for airway bypass versus 11·2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1·00 [Bayesian success threshold >0·95]).

Interpretation

Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema.

Funding

Broncus Technologies.

Introduction

Surgery to reduce lung volume in patients with pulmonary emphysema can increase residual volume (RV) and improve breathing mechanics and dyspnoea, even in individuals with homogeneous disease. However, with substantial surgical morbidity, adoption of this procedure has been low.1, 2, 3

Airway bypass is a bronchoscopic procedure to reduce lung volume that is designed for treatment of severe homogeneous emphysema. With this technique, passages are created in the bronchial airways to deflate air trapped in the emphysematous regions, and paclitaxel-eluting stents are placed to maintain passageway patency.4, 5 In preclinical, ex-vivo, and pretransplant studies, airway bypass released trapped air by bronchoscopic creation of transbronchial passageways.5, 6, 7, 8 In a feasibility study,5 efficacy was shown for airway bypass at 6 months in patients with a ratio of RV to total lung capacity (TLC) of more than 67%, a proportion that is also predictive of improvement in forced vital capacity (FVC) after lung-volume reduction surgery.9

The Exhale drug-eluting stent (Broncus Technologies, Mountain View, CA, USA) is composed of stainless steel and silicone and contains paclitaxel, which is intended to inhibit fibrotic responses.7 We designed the Exhale airway stents for emphysema (EASE) trial to investigate safety and efficacy of airway bypass for patients with severe homogeneous emphysema.

Section snippets

Participants

We undertook a multicentre, double-blind, randomised, sham-controlled trial at 38 specialist respiratory centres worldwide. The adaptive study design of the EASE trial and screening process to select patients with severe homogeneous disease has been published previously.10

Panel 1 summarises key inclusion and exclusion criteria. We focused inclusion criteria on definition of a population with severe hyperinflation. All participants had to undergo at least 6 weeks of pulmonary rehabilitation

Results

Between Oct 18, 2006, and April 8, 2009, 1522 people were screened for the study and 319 underwent randomisation. 212 participants were randomly assigned airway bypass (four were allocated after enrolment closed so did not receive the intervention) and 107 were allocated sham control (figure 1). 6-month follow-up data were available for 195 (94%) patients in the airway bypass arm and 90 (84%) who were assigned sham control. Seven (3%) participants in the airway bypass arm and seven (7%) who

Discussion

Findings of the EASE trial showed that at day 1, airway bypass released trapped gas from hyperinflated regions, thereby improving pulmonary function. However, durability was limited by pulmonary function tests and subjective, functional, and post-hoc CT measures. Outcomes for sham control and airway bypass were similar at months 3, 6, and 12. Although the EASE trial failed to show a difference between treatment arms with respect to the 6-month primary efficacy endpoint, invaluable lessons were

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See end of report for details of the EASE trial study group

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