The Long-Term Oxygen Treatment Trial for Chronic Obstructive Pulmonary Disease: Rationale, Design, and Lessons Learned
Roger D Yusen, Gerard J Criner, Alice L Sternberg, David H Au, Anne L Fuhlbrigge, Richard K Albert, Richard Casaburi, James K Stoller, Kathleen F Harrington, J Allen D Cooper Jr, Philip Diaz, Steven Gay, Richard Kanner, Neil MacIntyre, Fernando J Martinez, Steven Piantadosi, Frank Sciurba, David Shade, Thomas Stibolt, James Tonascia, Robert Wise, William C Bailey, LOTT Research Group *, LOTT Research Group, William C Bailey, Anne L Fuhlbrigge, Ernestina Sampong, Karin Sloan, Ashley Wagner, Susan Anderson, Marilyn Moy, Osarenoma Okunbor, James K Stoller, Scott Marlow, Yvonne Meli, Richard Rice, Loutfi S Aboussouan, Robert Castele, Joseph Parambil, Sumita Khatri, Aman Pande, Joe Zein, Thomas Olbrych, Stephan Alkins, Christine Jocko, Franck Rahaghi, Jean Barton, Richard K Albert, Jennifer Underwood, Barry Make, Jennifer Underwood, Neil MacIntyre, John Davies, Thomas Stibolt, Richard Mularski, Allison Naleway, Sarah Vertrees, Richard Casaburi, Janos Porszasz, Peggy Walker, Renee Indelicato, Lennard Specht, Kathleen Ellstrom, Jamie Portillo, David Horak, Brian Tiep, Mary Barnett, Philip Diaz, Janice Drake, Mahasti Rittinger, Rachael Compton, Scott Miller, Ralph J Panos, Laura A Lach, Gerard Criner, Carla Grabianowski, Francis Cordova, Parag Desai, Samuel Krachman, James Mamary, Nathaniel Marchetti, Aditi Satti, Eileen Mumm, Michelle Vega-Olivo, Jenny Hua, Vanna Tauch, Lii-Yoong Criner, Michael Jacobs, Peter Rising, Paul Simonelli, Michele Mitchell, Matthew Lammi, Connie Romaine, Howard Lee, Mary Ianacone, Steven Scharf, Wanda Bell-Farrell, M Jeffery Mador, Ayesha Rahman, Mumtaz Zaman, Lisa Hill, Alec Platt, J Allen Cooper, Kathleen Harrington, Mark Dransfield, Patti Smith, Donald Davis, J Allen Cooper, Patti Smith, Peruvemba Sriram, Katherine Herring, Steven Gay, Fernando Martinez, Meilan Han, Kelly Rysso, Catherine Meldrum, K P Ravikrishnan, Daniel Keena, Jennifer DeRidder, Beth Kring, Antonio Anzueto, Alex Aguilera, Timothy Houlihan, Reda Girgis, Jennifer Cannestra, Frank Sciurba, Benjamin Kelly, Richard Kanner, Mary Beth Scholand, G Martin Villegas, Judy Carle, David H Au, Edmunds Udris, Randall Curtis, David Au, Laura C Feemster, Richard Goodman, Brianna Moss, Lynn Reinke, Edmunds Udris, Moira Aitken, Bruce Culver, Roger D Yusen, Mario Castro, Brigitte Mittler, Jeanne Heaghney, Myron Jacobs, Min Joo, Nina Bracken, Edward Diamond, Mary K Joseph, Xavier Soler, Arianna Villa, Daniel Layish, Edwin Silverman, Roxanne Kelly, Daniel Cossette, James Tonascia, Patricia Belt, Amanda Blackford, Betty Collison, John Dodge, Michele Donithan, Cathleen Ewing, Rosetta Jackson, K Patrick May, Jill Meinert, Steven Piantadosi, Girlie Reyes, David Shade, Michael Smith, Alice L Sternberg, Mark Van Natta, Laura Wilson, Annette Wagoner, Robert Wise, Katherine P Yates, Rosemarie Hakim, Antonello Punturieri, Julie Bamdad, Thomas Croxton, Joanne Deshler, Pamela McCord-Reynolds, Mario Stylianou, Gail Weinmann, Gordon Bernard, James Anderson, Bernard Lo, Andrew Ries, Stuart Stoloff, Byron Thomashow, Barbara Tilley, Kevin Weiss, Roger D Yusen, Gerard J Criner, Alice L Sternberg, David H Au, Anne L Fuhlbrigge, Richard K Albert, Richard Casaburi, James K Stoller, Kathleen F Harrington, J Allen D Cooper Jr, Philip Diaz, Steven Gay, Richard Kanner, Neil MacIntyre, Fernando J Martinez, Steven Piantadosi, Frank Sciurba, David Shade, Thomas Stibolt, James Tonascia, Robert Wise, William C Bailey, LOTT Research Group *, LOTT Research Group, William C Bailey, Anne L Fuhlbrigge, Ernestina Sampong, Karin Sloan, Ashley Wagner, Susan Anderson, Marilyn Moy, Osarenoma Okunbor, James K Stoller, Scott Marlow, Yvonne Meli, Richard Rice, Loutfi S Aboussouan, Robert Castele, Joseph Parambil, Sumita Khatri, Aman Pande, Joe Zein, Thomas Olbrych, Stephan Alkins, Christine Jocko, Franck Rahaghi, Jean Barton, Richard K Albert, Jennifer Underwood, Barry Make, Jennifer Underwood, Neil MacIntyre, John Davies, Thomas Stibolt, Richard Mularski, Allison Naleway, Sarah Vertrees, Richard Casaburi, Janos Porszasz, Peggy Walker, Renee Indelicato, Lennard Specht, Kathleen Ellstrom, Jamie Portillo, David Horak, Brian Tiep, Mary Barnett, Philip Diaz, Janice Drake, Mahasti Rittinger, Rachael Compton, Scott Miller, Ralph J Panos, Laura A Lach, Gerard Criner, Carla Grabianowski, Francis Cordova, Parag Desai, Samuel Krachman, James Mamary, Nathaniel Marchetti, Aditi Satti, Eileen Mumm, Michelle Vega-Olivo, Jenny Hua, Vanna Tauch, Lii-Yoong Criner, Michael Jacobs, Peter Rising, Paul Simonelli, Michele Mitchell, Matthew Lammi, Connie Romaine, Howard Lee, Mary Ianacone, Steven Scharf, Wanda Bell-Farrell, M Jeffery Mador, Ayesha Rahman, Mumtaz Zaman, Lisa Hill, Alec Platt, J Allen Cooper, Kathleen Harrington, Mark Dransfield, Patti Smith, Donald Davis, J Allen Cooper, Patti Smith, Peruvemba Sriram, Katherine Herring, Steven Gay, Fernando Martinez, Meilan Han, Kelly Rysso, Catherine Meldrum, K P Ravikrishnan, Daniel Keena, Jennifer DeRidder, Beth Kring, Antonio Anzueto, Alex Aguilera, Timothy Houlihan, Reda Girgis, Jennifer Cannestra, Frank Sciurba, Benjamin Kelly, Richard Kanner, Mary Beth Scholand, G Martin Villegas, Judy Carle, David H Au, Edmunds Udris, Randall Curtis, David Au, Laura C Feemster, Richard Goodman, Brianna Moss, Lynn Reinke, Edmunds Udris, Moira Aitken, Bruce Culver, Roger D Yusen, Mario Castro, Brigitte Mittler, Jeanne Heaghney, Myron Jacobs, Min Joo, Nina Bracken, Edward Diamond, Mary K Joseph, Xavier Soler, Arianna Villa, Daniel Layish, Edwin Silverman, Roxanne Kelly, Daniel Cossette, James Tonascia, Patricia Belt, Amanda Blackford, Betty Collison, John Dodge, Michele Donithan, Cathleen Ewing, Rosetta Jackson, K Patrick May, Jill Meinert, Steven Piantadosi, Girlie Reyes, David Shade, Michael Smith, Alice L Sternberg, Mark Van Natta, Laura Wilson, Annette Wagoner, Robert Wise, Katherine P Yates, Rosemarie Hakim, Antonello Punturieri, Julie Bamdad, Thomas Croxton, Joanne Deshler, Pamela McCord-Reynolds, Mario Stylianou, Gail Weinmann, Gordon Bernard, James Anderson, Bernard Lo, Andrew Ries, Stuart Stoloff, Byron Thomashow, Barbara Tilley, Kevin Weiss
Abstract
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. Clinical trial registered with clinicaltrials.gov (NCT00692198).
Keywords: chronic obstructive pulmonary disease; hypoxemia; oxygen; randomized controlled trial; survival.
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Source: PubMed