학술논문
I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations
Document Type
article
Author
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; Aggarwal, Neil
Source
BMJ Open. 12(6)
Subject
Language
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.