1Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania2St. Joseph's Hospital and Medical Center, Phoenix, Arizona3University of Alabama at Birmingham UAB Lung Health Center, Birmingham, Alabama4Department of Medicine, University of Louisville, Louisville, Kentucky5Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania6Royal Brompton Hospital and Imperial College, London, United Kingdom7Duke University Medical Center, Duke University, Durham, North Carolina8Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil9Division of Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, Sacramento, California10Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil11University of California, San Francisco, San Francisco, California12Interventional Pulmonology, Beth Israel Deaconess Medical Center, Boston, Massachusetts13Medical University of South Carolina, Charleston, South Carolina14Pulmonary Critical Care and Sleep Medicine Consultants, Houston Methodist, Houston, Texas15Orlando Health Pulmonary and Sleep Medicine Group, Orlando Regional Medical Center, Orlando, Florida16Keck School of Medicine, University of Southern California, Los Angeles, California17Center for Major Airway Diseases, Cleveland Clinic, Cleveland Clinic Foundation, Respiratory Institute, Cleveland, Ohio18Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles, Torrance, California19Stanford Hospital and Clinics, Stanford, California20University Hospital Bristol NHS Foundation Trust, Bristol, United Kingdom21Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff, United Kingdom22Division of Cardiothoracic Surgery, Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois23Palo Alto Medical Foundation, El Camino Hospital, Mountain View, California24QST Consultations Ltd., Allendale, Michigan25Pulmonx Corporation, Redwood City, California; and26Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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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 ΔEBV-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 ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-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 ΔEBV-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.Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).