A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE)
Gerard J Criner, Richard Sue, Shawn Wright, Mark Dransfield, Hiram Rivas-Perez, Tanya Wiese, Frank C Sciurba, Pallav L Shah, Momen M Wahidi, Hugo Goulart de Oliveira, Brian Morrissey, Paulo F G Cardoso, Steven Hays, Adnan Majid, Nicholas Pastis Jr, Lisa Kopas, Mark Vollenweider, P Michael McFadden, Michael Machuzak, David W Hsia, Arthur Sung, Nabil Jarad, Malgorzata Kornaszewska, Stephen Hazelrigg, Ganesh Krishna, Brian Armstrong, Narinder S Shargill, Dirk-Jan Slebos, LIBERATE Study Group, Gerard J Criner, Francis Cordova, Parag Desai, Nathaniel Marchetti, Victor Kim, Kartik Shenoy, John Travaline, Jiji Thomas, Lii-Yoong H Criner, Richard Sue, Shawn Wright, Aaron Thornburg, Terry Thomas, Mark Dransfield, Surya Bhatt, James Michael Wells, Necole Seabron-Harris, Hiram Rivas-Perez, Umair Gauhar, Tanya Wiese, Crissie Despirito, Frank Sciurba, Jessica Bon Field, Divay Chandra, Joseph Leader, Roy Semaan, Christina Ledezma, Pallav Shah, Samuel Kemp, Justin Garner, Arafa Aboelhassan, Karthi Srikanthan, Eric Tenda, Anita Abraham, Cai Sim, Momen Wahidi, Kamran Mahmood, Scott Shofer, Kathleen Coles, Hugo Goulart de Oliveira, Guilherme Augusto Oliveira, Betina Machado, Igor Benedetto, Fabio Svartman, Amarilio de Macedo Neto, Leonardo Schreiner, Taiane Vieira, Brian Morrissey, Ken Yoneda, Tina Tham, Daniel Tompkins, Paulo F Guerreiro Cardoso, Rodrigo Athanazio, Felipe Nominando, Samia Rached, Luciana Cassimiro, Steven Hays, Eric Seeley, Pavan Shrestha, Gabriela R Dincheva, Adnan Majid, Daniel Alape-Moya, Mihir Parikh, Alichia Paton, Alexis Agnew, Nicholas Pastis Jr, Charlie Strange, Tatsiana Beiko, Danielle Woodford, Mary Blanton, Lisa Kopas, Timothy Connolly, Jose Fernando Santacruz, Bhavin Shah, Mark Vollenweider, Luis Herrera, Rumi Khan, Kristine Sernulka, P Michael McFadden, Richard Barbers, Michelle Hernandez, Michael Machuzak, Francisco Almeida, Joseph Cicenia, Thomas Gildea, Atul Mehta, Sonali Sethi, Yvonne Meli, David Hsia, Richard Casaburi, William Stringer, Leticia Diaz, Arthur Sung, Meghan Ramsey, Ryan Van Wert, Karen Morris, Nabil Jarad, Tim Batchelor, Iara Sequeiros, Katy Tucker, Malgorzata Kornaszweska, Hazem Fallouh, Ramsey Sabit, Hatam Naase, Joseph George, Azin Salimian, Helen Dyer, Stephen Hazelrigg, Kristal Adams, Karen Bade, Ganesh Krishna, Bryan S Benn, Michelle Canfield, Sharmila Vetri Villalan, Travis Stewart, Dirk-Jan Slebos, Nick H T Ten Hacken, Karin Klooster, Jorine Hartman, Sonja Augustijn, Gerard J Criner, Richard Sue, Shawn Wright, Mark Dransfield, Hiram Rivas-Perez, Tanya Wiese, Frank C Sciurba, Pallav L Shah, Momen M Wahidi, Hugo Goulart de Oliveira, Brian Morrissey, Paulo F G Cardoso, Steven Hays, Adnan Majid, Nicholas Pastis Jr, Lisa Kopas, Mark Vollenweider, P Michael McFadden, Michael Machuzak, David W Hsia, Arthur Sung, Nabil Jarad, Malgorzata Kornaszewska, Stephen Hazelrigg, Ganesh Krishna, Brian Armstrong, Narinder S Shargill, Dirk-Jan Slebos, LIBERATE Study Group, Gerard J Criner, Francis Cordova, Parag Desai, Nathaniel Marchetti, Victor Kim, Kartik Shenoy, John Travaline, Jiji Thomas, Lii-Yoong H Criner, Richard Sue, Shawn Wright, Aaron Thornburg, Terry Thomas, Mark Dransfield, Surya Bhatt, James Michael Wells, Necole Seabron-Harris, Hiram Rivas-Perez, Umair Gauhar, Tanya Wiese, Crissie Despirito, Frank Sciurba, Jessica Bon Field, Divay Chandra, Joseph Leader, Roy Semaan, Christina Ledezma, Pallav Shah, Samuel Kemp, Justin Garner, Arafa Aboelhassan, Karthi Srikanthan, Eric Tenda, Anita Abraham, Cai Sim, Momen Wahidi, Kamran Mahmood, Scott Shofer, Kathleen Coles, Hugo Goulart de Oliveira, Guilherme Augusto Oliveira, Betina Machado, Igor Benedetto, Fabio Svartman, Amarilio de Macedo Neto, Leonardo Schreiner, Taiane Vieira, Brian Morrissey, Ken Yoneda, Tina Tham, Daniel Tompkins, Paulo F Guerreiro Cardoso, Rodrigo Athanazio, Felipe Nominando, Samia Rached, Luciana Cassimiro, Steven Hays, Eric Seeley, Pavan Shrestha, Gabriela R Dincheva, Adnan Majid, Daniel Alape-Moya, Mihir Parikh, Alichia Paton, Alexis Agnew, Nicholas Pastis Jr, Charlie Strange, Tatsiana Beiko, Danielle Woodford, Mary Blanton, Lisa Kopas, Timothy Connolly, Jose Fernando Santacruz, Bhavin Shah, Mark Vollenweider, Luis Herrera, Rumi Khan, Kristine Sernulka, P Michael McFadden, Richard Barbers, Michelle Hernandez, Michael Machuzak, Francisco Almeida, Joseph Cicenia, Thomas Gildea, Atul Mehta, Sonali Sethi, Yvonne Meli, David Hsia, Richard Casaburi, William Stringer, Leticia Diaz, Arthur Sung, Meghan Ramsey, Ryan Van Wert, Karen Morris, Nabil Jarad, Tim Batchelor, Iara Sequeiros, Katy Tucker, Malgorzata Kornaszweska, Hazem Fallouh, Ramsey Sabit, Hatam Naase, Joseph George, Azin Salimian, Helen Dyer, Stephen Hazelrigg, Kristal Adams, Karen Bade, Ganesh Krishna, Bryan S Benn, Michelle Canfield, Sharmila Vetri Villalan, Travis Stewart, Dirk-Jan Slebos, Nick H T Ten Hacken, Karin Klooster, Jorine Hartman, Sonja Augustijn
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).
Trial registration: ClinicalTrials.gov NCT01796392.
Keywords: chronic obstructive pulmonary disease; emphysema; lung reduction.
Source: PubMed