Gerard J Criner1, Richard Sue2, Shawn Wright2, Mark Dransfield3, Hiram Rivas-Perez4, Tanya Wiese4, Frank C Sciurba5, Pallav L Shah6, Momen M Wahidi7, Hugo Goulart de Oliveira8, Brian Morrissey9, Paulo F G Cardoso10, Steven Hays11, Adnan Majid12, Nicholas Pastis13, Lisa Kopas14, Mark Vollenweider15, P Michael McFadden16, Michael Machuzak17, David W Hsia18, Arthur Sung19, Nabil Jarad20, Malgorzata Kornaszewska21, Stephen Hazelrigg22, Ganesh Krishna23, Brian Armstrong24, Narinder S Shargill25, Dirk-Jan Slebos26. 1. 1 Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania. 2. 2 St. Joseph's Hospital and Medical Center, Phoenix, Arizona. 3. 3 University of Alabama at Birmingham UAB Lung Health Center, Birmingham, Alabama. 4. 4 Department of Medicine, University of Louisville, Louisville, Kentucky. 5. 5 Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 6. 6 Royal Brompton Hospital and Imperial College, London, United Kingdom. 7. 7 Duke University Medical Center, Duke University, Durham, North Carolina. 8. 8 Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. 9. 9 Division of Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, Sacramento, California. 10. 10 Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil. 11. 11 University of California, San Francisco, San Francisco, California. 12. 12 Interventional Pulmonology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 13. 13 Medical University of South Carolina, Charleston, South Carolina. 14. 14 Pulmonary Critical Care and Sleep Medicine Consultants, Houston Methodist, Houston, Texas. 15. 15 Orlando Health Pulmonary and Sleep Medicine Group, Orlando Regional Medical Center, Orlando, Florida. 16. 16 Keck School of Medicine, University of Southern California, Los Angeles, California. 17. 17 Center for Major Airway Diseases, Cleveland Clinic, Cleveland Clinic Foundation, Respiratory Institute, Cleveland, Ohio. 18. 18 Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles, Torrance, California. 19. 19 Stanford Hospital and Clinics, Stanford, California. 20. 20 University Hospital Bristol NHS Foundation Trust, Bristol, United Kingdom. 21. 21 Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff, United Kingdom. 22. 22 Division of Cardiothoracic Surgery, Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois. 23. 23 Palo Alto Medical Foundation, El Camino Hospital, Mountain View, California. 24. 24 QST Consultations Ltd., Allendale, Michigan. 25. 25 Pulmonx Corporation, Redwood City, California; and. 26. 26 Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Abstract
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).
RCT Entities:
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).
Authors: Rene S Bermea; Joseph Miller; W Wyatt Wilson; Karen Dugan; Laura Frye; Septimiu Murgu; D Kyle Hogarth Journal: Am J Respir Crit Care Med Date: 2019-11-15 Impact factor: 21.405
Authors: Wassim W Labaki; Lucas M Kimmig; Gökhan M Mutlu; MeiLan K Han; Surya P Bhatt Journal: Am J Respir Crit Care Med Date: 2019-06-15 Impact factor: 21.405
Authors: Muhanned Abu-Hijleh; Kim Styrvoky; Vikram Anand; Fernando Woll; Lonny Yarmus; Michael S Machuzak; Daniel A Nader; Timothy W Mullett; D Kyle Hogarth; Jennifer W Toth; Ghazwan Acash; Roberto F Casal; Stephen Hazelrigg; Douglas E Wood Journal: Lung Date: 2019-08-28 Impact factor: 2.584
Authors: Jorrit B A Welling; Karin Klooster; Jean-Paul Charbonnier; Eva M Van Rikxoort; Clemens R M Barends; Huib A M Kerstjens; Nick H T Ten Hacken; Jorine E Hartman; Dirk-Jan Slebos Journal: Respiration Date: 2019-09-03 Impact factor: 3.580
Authors: Jorrit B A Welling; Jorine E Hartman; Nick H T Ten Hacken; Sonja W S Augustijn; Huib A M Kerstjens; Dirk-Jan Slebos; Karin Klooster Journal: Lung Date: 2019-08-31 Impact factor: 2.584