Twelve-month positive outcomes of Zephyr endobronchial valves in severe emphysema patients:LIBERATE trial

Introduction: Zephyr® Endobronchial Valve (EBV®) treatment in severe emphysema patients, improves lung function, exercise capacity and quality of life. Objective: Evaluate effectiveness and safety of EBV treatment in severe emphysema. Methods: 190 severe heterogeneous emphysema subjects (M47%/F53%) with hyperinflation (FEV1 27.4 %pred; RV 224.5 %pred) and absent collateral ventilation (Chartis®) were randomized 2:1 (EBV:Standard-of-Care (SoC). Responders were classified according to established Minimal Clinically Important Differences for outcome measures. Results: At 12-months 84.2% EBV subjects had a target lobe volume reduction ≥350mL. Between group differences (ΔEBV–SoC) for mean changes from baseline were significant (p<0.05) at 12 months: ΔFEV1= +0.106L (17.6%); ΔSGRQ= -7.1 points; ΔBODE Index= -1.2 points; and Δ6MWD= +39.3m. Responder rates significantly favored EBV over SoC for all measures. Major serious adverse events in the EBV group <45 days post-procedure were pneumothorax (EBV 26.6% vs SoC 0%), COPD exacerbations (7.8% vs 4.8%), and death (3.1% vs 0%). Between 45-days out to 12-months, these were COPD exacerbations (23.0% vs 30.6%) and death (0.8% vs 1.6%). Conclusions: Zephyr EBV treatment provides durable, clinically meaningful improvements in lung function, exercise capacity, dyspnea and quality of life in hyperinflated, severe emphysema patients with absent collateral ventilation

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE)

Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. Methods: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the Delta EBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. Measurements and Main Results: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a Delta FEV1 greater than or equal to 15% (P <0.001). DEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P <0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant DEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P <0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P <0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. Conclusions: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe