1. I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations
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Carolyn S Calfee, Michael A Matthay, Paul Henderson, Martin Eklund, Laura J Esserman, Chirag Patel, Angela Haczku, Michelle Jung, Tony Oliver, Alessio Crippa, Andrea Discacciati, Kathleen D Liu, Ellen L Burnham, Nuala J Meyer, Fady A Youssef, Derek W Russell, Julie Lang, Kevin W Gibbs, Daniel C Files, Sheetal Gandotra, Purnema Madahar, Nathan K Cobb, Timothy E Albertson, Rajiv Sonti, John P Reilly, Alejandra Jauregui, Iván García, Luis E Huerta, Daniel Clark Files, Neil R Aggarwal, Adam L Asare, Jeremy R Beitler, Paul A Berger, George Cimino, Melissa H Coleman, Paul T Henderson, Caroline A G Ittner, Kashif T Khan, Jonathan L Koff, Mary LaRose, Joe Levitt, Ruixiao Lu, Jeffrey D McKeehan, Karl W Thomas, Aaron M Mittel, Albert F Yen, Alexis E Suarez, Alexis L Serra, Alpesh N Amin, Amanda Rosen, Amy L Dzierba, Anna D Barker, Ariel R Weisman, Brian M Daniel, Brian M Morrissey, Caroline AG Ittner, Chayse Jones, Christina Creel-Bulos, Christina M Angelucci, Diana Ng, Fredy Chaparro-Rojas, Gavin H Harris, Harsh V Barot, Heny Su, Jacqueline B Sutter, Jamal Dodin, Jerry S Lee, John Kazianis, Joshua F Detelich, Julie E Lang, Justin Muir, Katarzyna Gosek, Katherine L Nugent, Kimberly Yee, Laura G Rodrigues, Laura R Macias, Lindsey A Orr, Lindsie L Boerger, Lissette Rosario-Remigio, Lucia Kufa, Maged Tanios, Maria B Reyes, Max W Adelman, Maya M Juarez, Michelle Meyers, Mitchell P Sternlieb, Neil Aggarwal, Nilam S Mangalmurti, Patrice Jones, Paul L Saban, Peter S Marshall, Philiip A Robinson, Philip Yang, Rahul Nair, Richard Anthony Lee, Richard G Wunderink, Romina Wahab, Roxana A Lupu, Santhi I Kumar, Sara C Auld, Scott Fields, Se Fum Wong, Skyler J Pearson, Spencer Whealon, Timothy F Obermiller, Anita Darmanian, John Schicchi, Esmeralda Martinez, Farjad Sarafian, Julie Nguyen, Bethany Weiler-Lisowski, Jaime Wyatt, Daniel Blevins, Marylee Melendrez, Brenda Lopez, Hiwet Tzehaie, Omowunmi Amosu, Austin Simonson, Erin Hardy, Brett Lindgren, Gregory Peterfreund, Leigha Landreth, and Lisa Parks
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Medicine - Abstract
Introduction The 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 analysis The 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 dissemination ISPY 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 number NCT04488081.
- Published
- 2022
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