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

Publication ,  Journal Article
Casey, JD; Johnson, NJ; Semler, MW; Collins, SP; Aggarwal, NR; Brower, RG; Chang, SY; Eppensteiner, J; Filbin, M; Gibbs, KW; Ginde, AA ...
Published in: Ann Am Thorac Soc
September 2020

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).

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Published In

Ann Am Thorac Soc

DOI

EISSN

2325-6621

Publication Date

September 2020

Volume

17

Issue

9

Start / End Page

1144 / 1153

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Single-Blind Method
  • SARS-CoV-2
  • Pneumonia, Viral
  • Pandemics
  • Hydroxychloroquine
  • Humans
  • Hospitalization
  • Dose-Response Relationship, Drug
  • Coronavirus Infections
 

Citation

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Casey, J. D., Johnson, N. J., Semler, M. W., Collins, S. P., Aggarwal, N. R., Brower, R. G., … Self, W. H. (2020). Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19. Ann Am Thorac Soc, 17(9), 1144–1153. https://doi.org/10.1513/AnnalsATS.202005-478SD
Casey, Jonathan D., Nicholas J. Johnson, Matthew W. Semler, Sean P. Collins, Neil R. Aggarwal, Roy G. Brower, Steven Y. Chang, et al. “Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.Ann Am Thorac Soc 17, no. 9 (September 2020): 1144–53. https://doi.org/10.1513/AnnalsATS.202005-478SD.
Casey JD, Johnson NJ, Semler MW, Collins SP, Aggarwal NR, Brower RG, et al. Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19. Ann Am Thorac Soc. 2020 Sep;17(9):1144–53.
Casey, Jonathan D., et al. “Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.Ann Am Thorac Soc, vol. 17, no. 9, Sept. 2020, pp. 1144–53. Pubmed, doi:10.1513/AnnalsATS.202005-478SD.
Casey 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, Thompson BT, Brown SM, Self WH. Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19. Ann Am Thorac Soc. 2020 Sep;17(9):1144–1153.

Published In

Ann Am Thorac Soc

DOI

EISSN

2325-6621

Publication Date

September 2020

Volume

17

Issue

9

Start / End Page

1144 / 1153

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Single-Blind Method
  • SARS-CoV-2
  • Pneumonia, Viral
  • Pandemics
  • Hydroxychloroquine
  • Humans
  • Hospitalization
  • Dose-Response Relationship, Drug
  • Coronavirus Infections