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Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.

TitleRationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.
Publication TypeJournal Article
Year of Publication2020
AuthorsCasey JD, Johnson NJ, Semler MW, Collins SP, Aggarwal NR, Brower RG, Chang SY, Eppensteiner J, Filbin M, Gibbs KW, Ginde AA, Gong MN, Harrell F, Hayden DL, Hough CL, Khan A, Leither LM, Moss M, Oldmixon CF, Park PK, Reineck LA, Ringwood NJ, Robinson BRH, Schoenfeld DA, Shapiro NI, Steingrub JS, Torr DK, Weissman A, Lindsell CJ, Rice TW, B Thompson T, Brown SM, Self WH
JournalAnn Am Thorac Soc
Volume17
Issue9
Pagination1144-1153
Date Published2020 Sep
ISSN2325-6621
KeywordsAdult, Antimalarials, Betacoronavirus, Coronavirus Infections, COVID-19, Dose-Response Relationship, Drug, Hospitalization, Humans, Hydroxychloroquine, Pandemics, Pneumonia, Viral, SARS-CoV-2, Single-Blind Method, Treatment Outcome
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 ) widespread, off-label use of the study drug before the availability of safety and efficacy data; ) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; ) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; ) obtaining indistinguishable drug and placebo without delaying enrollment; and ) 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).

DOI10.1513/AnnalsATS.202005-478SD
Alternate JournalAnn Am Thorac Soc
PubMed ID32492354
PubMed Central IDPMC7462324
Grant ListU01 HL123018 / HL / NHLBI NIH HHS / United States
U01 HL123031 / HL / NHLBI NIH HHS / United States
K23 HL143053 / HL / NHLBI NIH HHS / United States
U01 HL123020 / HL / NHLBI NIH HHS / United States
U01 HL122989 / HL / NHLBI NIH HHS / United States
U01 HL123009 / HL / NHLBI NIH HHS / United States
U01 HL123004 / HL / NHLBI NIH HHS / United States
U01 HL123008 / HL / NHLBI NIH HHS / United States
U01 HL123022 / HL / NHLBI NIH HHS / United States
U01 HL123027 / HL / NHLBI NIH HHS / United States
K12 HL133117 / HL / NHLBI NIH HHS / United States
U01 HL123023 / HL / NHLBI NIH HHS / United States
T32 HL087738 / HL / NHLBI NIH HHS / United States
U01 HL122998 / HL / NHLBI NIH HHS / United States
UL1 TR002243 / TR / NCATS NIH HHS / United States
U01 HL123033 / HL / NHLBI NIH HHS / United States
U01 HL123010 / HL / NHLBI NIH HHS / United States
R01 HL144624 / HL / NHLBI NIH HHS / United States
K23 HL153584 / HL / NHLBI NIH HHS / United States