A multicenter RCT of Zephyr® Endobronchial Valve treatment in heterogeneous emphysema (LIBERATE).

RATIONALE: This is the first multicenter RCT to evaluate effectiveness and safety of Zephyr® Endobronchial Valve EBV® out to 12-months.OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation (CV) 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 ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of ≥15%. Secondary endpoints included absolute changes in post-BD FEV1, Six-Minute Walk Distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ) scores.

RESULTS: 190 subjects, 128 EBV and 62 SoC were randomized. At 12-months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 ≥15% (p<0.001). ΔEBV-SoC at 12-months was statistically and clinically significant: for FEV1 (L), 0.106L (p<0.001); 6MWD, +39.31m (p=0.002); and SGRQ, -7.05 points (p=0.004). Significant ΔEBV-SoC were also observed in hyperinflation (RV, -522ml; p<0.001), mMRC, -0.8 points (p<0.001), and the BODE Index (-1.2 points). Pneumothorax was the most common serious adverse event in the Treatment Period (procedure to 45 days), 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. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01796392.