I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations

Daniel Clark Files; Michael A Matthay; Carolyn S Calfee; Neil R Aggarwal; Adam L Asare; Jeremy R Beitler; Paul A Berger; Ellen L Burnham; George Cimino; Melissa H Coleman; Alessio Crippa; Andrea Discacciati; Sheetal Gandotra; Kevin W Gibbs; Paul T Henderson; Caroline A G Ittner; Alejandra Jauregui; Kashif T Khan; Jonathan L Koff; Julie Lang; Mary LaRose; Joe Levitt; Ruixiao Lu; Jeffrey D McKeehan; Nuala J Meyer; Derek W Russell; Karl W Thomas; Martin Eklund; Laura J Esserman; Kathleen D Liu; ISPY COVID Adaptive Platform Trial Network; undefined

doi:10.1136/bmjopen-2021-060664

I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations

BMJ Open. 2022 Jun 6;12(6):e060664. doi: 10.1136/bmjopen-2021-060664.

Authors

Daniel Clark Files¹, Michael A Matthay², Carolyn S Calfee², Neil R Aggarwal³, Adam L Asare⁴, Jeremy R Beitler⁵, Paul A Berger⁶, Ellen L Burnham³, George Cimino⁷, Melissa H Coleman², Alessio Crippa⁸, Andrea Discacciati⁹, Sheetal Gandotra¹⁰, Kevin W Gibbs¹¹, Paul T Henderson⁴, Caroline A G Ittner¹², Alejandra Jauregui², Kashif T Khan¹³, Jonathan L Koff¹⁴, Julie Lang¹³, Mary LaRose¹¹, Joe Levitt¹⁵, Ruixiao Lu⁷, Jeffrey D McKeehan¹⁶, Nuala J Meyer¹⁷, Derek W Russell¹⁸, Karl W Thomas¹¹, Martin Eklund¹⁹, Laura J Esserman², Kathleen D Liu²⁰; ISPY COVID Adaptive Platform Trial Network; undefined

Collaborators

Laura J Esserman, Carolyn S Calfee, Kathleen D Liu, Melissa H Coleman, Michael A Matthay, Jeremy R Beitler, Aaron M Mittel, Adam L Asare, Albert F Yen, Alejandra Jauregui, Alessio Crippa, Alexis E Suarez, Alexis L Serra, Alpesh N Amin, Amanda Rosen, Amy L Dzierba, Andrea Discacciati, Angela Haczku, Anna D Barker, Ariel R Weisman, Brian M Daniel, Brian M Morrissey, Caroline Ag Ittner, Chayse Jones, Christina Creel-Bulos, Christina M Angelucci, Daniel C Files, Derek W Russell, Diana Ng, Ellen L Burnham, Fady A Youssef, Fredy Chaparro-Rojas, Gavin H Harris, Harsh V Barot, Heny Su, Ivan Garcia, Jacqueline B Sutter, Jamal Dodin, Jeffrey D McKeehan, Jerry S Lee, John Kazianis, John P Reilly, Jonathan L Koff, Joshua F Detelich, Julie E Lang, Justin Muir, Karl W Thomas, Kashif T Khan, Katarzyna Gosek, Katherine L Nugent, Kevin W Gibbs, Kimberly Yee, Laura G Rodrigues, Laura R Macias, Lindsey A Orr, Lindsie L Boerger, Lissette Rosario-Remigio, Lucia Kufa, Luis E Huerta, Maged Tanios, Maria B Reyes, Martin Eklund, Mary LaRose, Max W Adelman, Maya M Juarez, Michelle Jung, Michelle Meyers, Mitchell P Sternlieb, Nathan K Cobb, Neil Aggarwal, Nilam S Mangalmurti, Nuala J Meyer, Patrice Jones, Paul A Berger, Paul Henderson, Paul L Saban, Peter S Marshall, Philiip A Robinson, Philip Yang, Purnema Madahar, Rahul Nair, Rajiv Sonti, Richard Anthony Lee, Richard G Wunderink, Romina Wahab, Roxana A Lupu, Ruixiao Lu, Santhi I Kumar, Sara C Auld, Scott Fields, Se Fum Wong, Sheetal Gandotra, Skyler J Pearson, Spencer Whealon, Timothy E Albertson, Timothy F Obermiller, Tony Oliver, 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, Chirag Patel, Joe Levitt, Erin Hardy, Brett Lindgren, Gregory Peterfreund, Leigha Landreth, Lisa Parks, Neil Aggarwal

Affiliations

¹ Pulmonary, Critical Care, Allergy and Immunology Division, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA Clark.Files@wakehealth.edu.
² University of California San Francisco, San Francisco, California, USA.
³ University of Colorado Denver School of Medicine, Aurora, Colorado, USA.
⁴ Quantum Leap Healthcare Collaborative, San Francisco, California, USA.
⁵ Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University, New York City, New York, USA.
⁶ Sanford USD Medical Center - Sioux Falls, Sioux Falls, South Dakota, USA.
⁷ Quantum Leap Healthcare Collaborative, Fremont, California, USA.
⁸ Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Stockholm, Sweden.
⁹ Karolinska Institute, Stockholm, Stockholm, Sweden.
¹⁰ Pulmonary, Allergy, Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹¹ Department of Medicine, Section of Pulmonary, Critical Care, Allergy and Immunologic Disease, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
¹² University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
¹³ University of Southern California, Los Angeles, California, USA.
¹⁴ Yale School of Medicine, New Haven, Connecticut, USA.
¹⁵ Stanford University, Stanford, California, USA.
¹⁶ University of Colorado, Denver, Colorado, USA.
¹⁷ Medicine, Division of Pulmonary, Allergy, & Critical Care Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁸ Division of Pulmonary, Allergy, & Critical Care Medicine, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
¹⁹ Karolinska Institutet, Stockholm, Sweden.
²⁰ Nephrology, University of California San Francisco, San Francisco, California, USA.

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.

Keywords: COVID-19; adult intensive & critical care; clinical trials.

Publication types

Randomized Controlled Trial
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Bayes Theorem
COVID-19*
Humans
Pandemics
Respiratory Distress Syndrome*
Respiratory Insufficiency*
SARS-CoV-2
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT04488081

Abstract

Publication types

MeSH terms

Associated data

Grants and funding