Author:
Files D. Clark,Matthay Michael A.,Calfee Carolyn S.,Aggarwal Neil,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 A.G.,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.
Abstract
AbstractIntroductionThe COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalized with severe COVID-19. The ISPY COVID 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 trial during the first phase of trial activity from April 2020 until December 2021.Methods and analysisThe ISPY COVID Trial is a multi-center open label phase 2 platform trial in the United States designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID Trial network includes academic and community hospitals with significant geographic diversity across the country. Enrolled patients are randomized 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 enrolls to a maximum of 125 patients per arm and is compared to concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrollment and adaptation of the trial design is ongoing.Ethics and disseminationISPY COVID 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 numberClinicaltrials.gov registration number NCT04488081Strengths and limitations of this studyThe ISPY COVID Trial was developed in early 2020 to rapidly and simultaneously evaluate therapeutics for severe COVID-19 on an adaptive open label phase 2 platformThe ISPY COVID Adaptive Platform Trial Network is an academic-industry partnership that includes academic and community hospitals spanning a wide geographic area across the United StatesOf December 2021, 11 investigational agent arms have been activated on the ISPY COVID Trial PlatformThe ISPY COVID Trial was designed to identify therapeutic agents with a large clinical effect for further testing in definitive efficacy trials—limitations to this approach include the risk of a type 2 error
Publisher
Cold Spring Harbor Laboratory