Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19
Year: 2020
Type: article
Study design: Study Protocol
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. Clinical trial registered with www.clinicaltrials.gov (NCT04332991).
Authors: Jonathan D. Casey, Nicholas J. Johnson, Matthew W. Semler, Sean P. Collins, Neil R. Aggarwal, Roy G. Brower, Steven Y. Chang, John Eppensteiner, Michael Filbin, Kevin W. Gibbs, Adit A. Ginde, Michelle N. Gong, Frank Harrell, Douglas L. Hayden, Catherine L. Hough, Akram Khan, Lindsay M. Leither, Marc Moss, Cathryn F. Oldmixon, Pauline K. Park, Lora A. Reineck, Nancy J. Ringwood, Bryce R. H. Robinson, David A. Schoenfeld, Nathan I. Shapiro, Jay S. Steingrub, Donna K. Torr, Alexandra Weissman, Christopher J. Lindsell, Todd W. Rice, B. Taylor Thompson, Samuel M. Brown, Wesley H. Self
Institutions: Harborview Medical Center, National Heart, Lung, and Blood Institute, Johns Hopkins University, University of California, Los Angeles, Duke University, Wake Forest University Health Sciences, Wake Forest University, Albert Einstein College of Medicine, Montefiore Medical Center, Vanderbilt University, Vanderbilt University Medical Center, Oregon Health & Science University, University of Utah, Intermountain Medical Center, University of Colorado Anschutz, University of Michigan, University of Washington, Beth Israel Deaconess Medical Center, Harvard University, University of Massachusetts Chan Medical School, University of Pittsburgh, Massachusetts General Hospital
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: Acute Lung Injury Group New England Program to Support PETAL Network Research, The Vanderbilt Emergency Care Research Training Program, CCC for NHLBI Prevention and Early Treatment of Acute Lung Injury PETAL Network, Pacific Northwest Clinical Center for the NHLBI PETAL Network, Intermountain Healthcare Clinical Center (CC) for the NHLBI Prevention and Early, Wake Forest Clinical Center for the NHLBI PETAL Network, Clinical Centers (CC) for the NHLBI Prevention and Early Treatment of Acute Lung, Bag-Mask Ventilation to PreVent Hypoxemia during Tracheal Intubation in the Emergency Department: A Clinical Trial, Ohio Consortium Clinical Center for the NHLBI Prevention and Early Treatment of A, Oxygen Saturation Targets during Mechanical Ventilation of Critically Ill Adults: A Clinical Trial, Study of Treatment's Echocardiographic Mechanisms (CLOVERS-STEM), Colorado PETAL Clinical Center, Einstein PETAL: Clinical Center for the PETAL Network, Clinical Centers (CC) for the NHLBI Prevention and Early Treatment of Acute Lung, Preventive and Early Treatment of Acute Lung Injury Clinical Trials Network- Pgh, Prevention and Early Treatment of Acute Lung Injury, Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network, Clinical and Translational Training Program in Pulmonary Medicine, Vanderbilt Institute for Clinical and Translational Research (VICTR)
OpenAlex ID: W3031453838