The long-term oxygen treatment trial for chronic obstructive pulmonary disease: Rationale, design, and lessons learned

Roger D. Yusen, Washington University School of Medicine in St. Louis
Gerard J. Criner, Temple University Hospital
Alice L. Sternberg, Johns Hopkins Bloomberg School of Public Health
David H. Au, University of Washington, Seattle
Anne L. Fuhlbrigge, COLORADO
Richard K. Albert, Denver Health Med Center
Richard Casaburi, Harbor-UCLA Medical Center
James K. Stoller, Cleveland Clinic Foundation
Kathleen F. Harrington, The University of Alabama at Birmingham
J. Allen D. Cooper, The University of Alabama at Birmingham
Philip Diaz, The Ohio State University
Steven Gay, University of Michigan Hospital
Richard Kanner, The University of Utah
Neil MacIntyre, Duke University Medical Center
Fernando J. Martinez, Weill Cornell Medicine
Steven Piantadosi, Johns Hopkins Bloomberg School of Public Health
Frank Sciurba, University of Pittsburgh
David Shade, Johns Hopkins Bloomberg School of Public Health
Thomas Stibolt, Kaiser Permanente Center for Health Research
James Tonascia, Johns Hopkins Bloomberg School of Public Health
Robert Wise, Johns Hopkins Bloomberg School of Public Health
William C. Bailey, The University of Alabama at Birmingham
Ernestina Sampong, Brigham and Women's Hospital
Karin Sloan, Boston Medical Center
Ashley Wagner, Boston Medical Center
Susan Anderson, Boston Medical Center
Marilyn Moy
Osarenoma Okunbor
Scott Marlow, Cleveland Clinic Foundation
Yvonne Meli, Cleveland Clinic Foundation
Richard Rice, Cleveland Clinic Foundation
Loutfi S. Aboussouan, Cleveland Clinic Foundation


Copyright © 2018 by the American Thoracic Society. The Long-Term Oxygen Treatment Trial demonstrated that long-term supplemental oxygen did not reduce time to hospital admission or death for patients who have stable chronic obstructive pulmonary disease and resting and/or exercise-induced moderate oxyhemoglobin desaturation, nor did it provide benefit for any other outcome measured in the trial. Nine months after initiation of patient screening, after randomization of 34 patients to treatment, a trial design amendment broadened the eligible population, expanded the primary outcome, and reduced the goal sample size. Within a few years, the protocol underwent minor modifications, and a second trial design amendment lowered the required sample size because of lower than expected treatment group crossover rates. After 5.5 years of recruitment, the trial met its amended sample size goal, and 1 year later, it achieved its follow-up goal. The process of publishing the trial results brought renewed scrutiny of the study design and the amendments. This article expands on the previously published design and methods information, provides the rationale for the amendments, and gives insight into the investigators' decisions about trial conduct. The story of the Long-Term Oxygen Treatment Trial may assist investigators in future trials, especially those that seek to assess the efficacy and safety of long-term oxygen therapy.