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.


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