Samuel V Kemp1,2, Dirk-Jan Slebos3, Alan Kirk4, Malgorzata Kornaszewska5, Kris Carron6, Lars Ek7, Gustav Broman8, Gunnar Hillerdal8, Herve Mal9, Christophe Pison10, Amandine Briault10, Nicola Downer2, Kaid Darwiche11, Jagan Rao12, Ralf-Harto Hübner13, Christof Ruwwe-Glosenkamp13, Valéry Trosini-Desert14, Ralf Eberhardt15, Felix J Herth15, Eric Derom16, Thomas Malfait16, Pallav L Shah1, Justin L Garner1, Nick H Ten Hacken3, Hazem Fallouh5, Sylvie Leroy17, Charles H Marquette17. 1. 1 Royal Brompton Hospital and Imperial College London, London, United Kingdom. 2. 2 Sherwood Forest Hospitals, NHS Foundation Trust, Nottinghamshire, United Kingdom. 3. 3 Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 4. 4 Department of Thoracic Surgery, West of Scotland Regional Heart & Lung Centre, Golden Jubilee National Hospital, West Dunbartonshire, Scotland, United Kingdom. 5. 5 Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff, United Kingdom. 6. 6 Department of Pulmonology, AZ Delta, Menen, Belgium. 7. 7 Department of Pulmonary Diseases, Skane University Hospital, Lund, Sweden. 8. 8 Department of Pulmonary Diseases, Uppsala University Hospital, Uppsala, Sweden. 9. 9 Service de Pneumologie A, Hôpital Bichat, Paris, France. 10. 10 Clinique Universitaire de Pneumologie, Pôle Thorax et Vaisseaux, CHU Grenoble Alpes, Grenoble, France. 11. 11 Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Clinic Essen, Essen, Germany. 12. 12 Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, United Kingdom. 13. 13 Charité Universitätsmedizin Berlin, Medizinische Klinik m. Schw. Infektiologie und Pneumologie, Campus Virchow, Berlin, Germany. 14. 14 Service de Pneumologie et Réanimation, Unité d'Endoscopie Bronchique, Groupe Hospitalier Pitié Salpétrière, Paris, France. 15. 15 Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg and Translational Lung Research Center Heidelberg, Heidelberg, Germany. 16. 16 Department of Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium; and. 17. 17 Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, FHU OncoAge, Service de Pneumologie, Nice, France.
Abstract
RATIONALE: Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach. OBJECTIVES: To evaluate the efficacy and safety of Zephyr EBVs in patients with heterogeneous emphysema and absence of collateral ventilation. METHODS: This was a prospective, multicenter 2:1 randomized controlled trial of EBVs plus standard of care or standard of care alone (SoC). Primary outcome at 3 months post-procedure was the percentage of subjects with FEV1 improvement from baseline of 12% or greater. Changes in FEV1, residual volume, 6-minute-walk distance, St. George's Respiratory Questionnaire score, andmodified Medical Research Council score were assessed at 3 and 6 months, and target lobe volume reduction on chest computed tomography at 3 months. MEASUREMENTS AND MAIN RESULTS:Ninety seven subjects were randomized to EBV (n = 65) or SoC (n = 32). At 3 months, 55.4% of EBV and 6.5% of SoC subjects had an FEV1 improvement of 12% or more (P < 0.001). Improvements were maintained at 6 months: EBV 56.3% versus SoC 3.2% (P < 0.001), with a mean ± SD change in FEV1 at 6 months of 20.7 ± 29.6% and -8.6 ± 13.0%, respectively. A total of 89.8% of EBV subjects had target lobe volume reduction greater than or equal to 350 ml, mean 1.09 ± 0.62 L (P < 0.001). Between-group differences for changes at 6 months were statistically and clinically significant: ΔEBV-SoC for residual volume, -700 ml; 6-minute-walk distance, +78.7 m; St. George's Respiratory Questionnaire score, -6.5 points; modified Medical Research Council dyspnea score, -0.6 points; and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, -1.8 points (all P < 0.05). Pneumothorax was the most common adverse event, occurring in 19 of 65 (29.2%) of EBV subjects. CONCLUSIONS:EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT02022683).
RCT Entities:
RATIONALE: Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach. OBJECTIVES: To evaluate the efficacy and safety of Zephyr EBVs in patients with heterogeneous emphysema and absence of collateral ventilation. METHODS: This was a prospective, multicenter 2:1 randomized controlled trial of EBVs plus standard of care or standard of care alone (SoC). Primary outcome at 3 months post-procedure was the percentage of subjects with FEV1 improvement from baseline of 12% or greater. Changes in FEV1, residual volume, 6-minute-walk distance, St. George's Respiratory Questionnaire score, and modified Medical Research Council score were assessed at 3 and 6 months, and target lobe volume reduction on chest computed tomography at 3 months. MEASUREMENTS AND MAIN RESULTS: Ninety seven subjects were randomized to EBV (n = 65) or SoC (n = 32). At 3 months, 55.4% of EBV and 6.5% of SoC subjects had an FEV1 improvement of 12% or more (P < 0.001). Improvements were maintained at 6 months: EBV 56.3% versus SoC 3.2% (P < 0.001), with a mean ± SD change in FEV1 at 6 months of 20.7 ± 29.6% and -8.6 ± 13.0%, respectively. A total of 89.8% of EBV subjects had target lobe volume reduction greater than or equal to 350 ml, mean 1.09 ± 0.62 L (P < 0.001). Between-group differences for changes at 6 months were statistically and clinically significant: ΔEBV-SoC for residual volume, -700 ml; 6-minute-walk distance, +78.7 m; St. George's Respiratory Questionnaire score, -6.5 points; modified Medical Research Council dyspnea score, -0.6 points; and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, -1.8 points (all P < 0.05). Pneumothorax was the most common adverse event, occurring in 19 of 65 (29.2%) of EBV subjects. CONCLUSIONS:EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT02022683).