Rationale and design of ORCHID: A randomized placebo-controlled clinical trial of hydroxychloroquine for adults hospitalized with COVID-19

ORCHID Protocol Committee and the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators

Research output: Contribution to journalArticlepeer-review

Abstract

The ORCHID (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease) trial is a multicenter, blinded, randomized trial of hydroxychloroquine versus placebo for the treatment of adults hospitalized with coronavirus disease (COVID-19). This document provides the rationale and background for the trial and highlights key design features. We discuss five novel challenges to the design and conduct of a large, multicenter, randomized trial during a pandemic, including 1) widespread, off-label use of the study drug before the availability of safety and efficacy data; 2) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; 3) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; 4) obtaining indistinguishable drug and placebo without delaying enrollment; and 5) rapidly obtaining administrative and regulatory approvals. Our goals in describing how the ORCHID trial progressed from study conception to enrollment of the first patient in 15 days are to inform the development of other high-quality, multicenter trials targeting COVID-19. We describe lessons learned to improve the efficiency of future clinical trials, particularly in the setting of pandemics. The ORCHID trial will provide high-quality, clinically relevant data on the safety and efficacy of hydroxychloroquine for the treatment of COVID-19 among hospitalized adults.

Original languageEnglish (US)
Pages (from-to)1144-1153
Number of pages10
JournalAnnals of the American Thoracic Society
Volume17
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • ARDS
  • COVID-19
  • Hydroxychloroquine
  • ORCHID
  • SARS-CoV-2

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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