1. I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations
- Author
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Files, Daniel Clark, Matthay, Michael A, Calfee, Carolyn S, Aggarwal, Neil R, Asare, Adam L, Beitler, Jeremy R, Berger, Paul A, Burnham, Ellen L, Cimino, George, Coleman, Melissa H, Crippa, Alessio, Discacciati, Andrea, Gandotra, Sheetal, Gibbs, Kevin W, Henderson, Paul T, Ittner, Caroline AG, Jauregui, Alejandra, Khan, Kashif T, Koff, Jonathan L, Lang, Julie, LaRose, Mary, Levitt, Joe, Lu, Ruixiao, McKeehan, Jeffrey D, Meyer, Nuala J, Russell, Derek W, Thomas, Karl W, Eklund, Martin, Esserman, Laura J, Liu, Kathleen D, Mittel, Aaron M, Yen, Albert F, Suarez, Alexis E, Serra, Alexis L, Amin, Alpesh N, Rosen, Amanda, Dzierba, Amy L, Haczku, Angela, Barker, Anna D, Weisman, Ariel R, Daniel, Brian M, Morrissey, Brian M, Jones, Chayse, Creel-Bulos, Christina, Angelucci, Christina M, Files, Daniel C, Ng, Diana, Youssef, Fady A, Chaparro-Rojas, Fredy, Harris, Gavin H, Barot, Harsh V, Su, Heny, Garcia, Ivan, Sutter, Jacqueline B, Dodin, Jamal, Lee, Jerry S, Kazianis, John, Reilly, John P, Detelich, Joshua F, Lang, Julie E, Muir, Justin, Gosek, Katarzyna, Nugent, Katherine L, Yee, Kimberly, Rodrigues, Laura G, Macias, Laura R, Orr, Lindsey A, Boerger, Lindsie L, Rosario-Remigio, Lissette, Kufa, Lucia, Huerta, Luis E, Tanios, Maged, Reyes, Maria B, Adelman, Max W, Juarez, Maya M, Jung, Michelle, Meyers, Michelle, Sternlieb, Mitchell P, Cobb, Nathan K, and Aggarwal, Neil
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Clinical Research ,Clinical Trials and Supportive Activities ,Good Health and Well Being ,Bayes Theorem ,COVID-19 ,Humans ,Pandemics ,Respiratory Distress Syndrome ,Respiratory Insufficiency ,SARS-CoV-2 ,Treatment Outcome ,ISPY COVID Adaptive Platform Trial Network ,undefined ,adult intensive & critical care ,clinical trials ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences - Abstract
IntroductionThe COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation and challenges of the ISPY COVID-19 trial during the first phase of trial activity from April 2020 until December 2021.Methods and analysisThe ISPY COVID-19 Trial is a multicentre open-label phase 2 platform trial in the USA designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID-19 Trial network includes academic and community hospitals with significant geographical diversity across the country. Enrolled patients are randomised to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes-time to recovery and mortality. The statistical design uses a Bayesian model with 'stopping' and 'graduation' criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrols to a maximum of 125 patients per arm and is compared with concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrolment and adaptation of the trial design are ongoing.Ethics and disseminationISPY COVID-19 operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer-reviewed medical journals.Trial registration numberNCT04488081.
- Published
- 2022