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

Area of Science:

• * Clinical trial design and methodology
• * Pharmaceutical research and development
• * Infectious disease therapeutics

Background:

• * The COVID-19 pandemic necessitated rapid development of effective treatments for hospitalized patients.
• * Existing therapeutic options for severe COVID-19 were limited, creating an urgent need for novel agents.
• * Early 2020 saw the initiation of adaptive platform trials to accelerate drug evaluation.

Purpose of the Study:

• * To outline the design, rationale, and implementation of the ISPY COVID-19 trial.
• * To describe the challenges encountered during the initial phase of trial operations (April 2020–December 2021).
• * To detail the adaptive platform strategy for evaluating multiple investigational agents simultaneously.

Main Methods:

• * A multicenter, open-label, phase 2 platform trial conducted in the USA.
• * Randomization of patients to investigational agents or a control arm.
• * Bayesian statistical design with adaptive 'stopping' and 'graduation' criteria.
• * Evaluation of primary outcomes: time to recovery and mortality.
• * Maximum enrollment of 125 patients per investigational agent arm.

Main Results:

• * As of December 2021, 11 investigational agent arms were activated, with 8 arms completed.
• * The trial network comprised geographically diverse academic and community hospitals.
• * Enrollment and trial design adaptation were ongoing.
• * The platform facilitated efficient evaluation and progression of promising therapies.

Conclusions:

• * The ISPY COVID-19 trial successfully implemented an adaptive platform for rapid COVID-19 therapeutic evaluation.
• * The trial design allowed for efficient discarding of ineffective agents and advancement of promising ones.
• * The platform's flexibility supported ongoing adaptation to evolving research needs during the pandemic.