Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing the coronavirus disease (COVID-19) pandemic. Currently, there is a lack of evidence-based therapies to prevent COVID-19 following exposure to the virus, or to prevent worsening of symptoms following confirmed infection. We describe the design of a clinical trial of hydroxychloroquine for post-exposure prophylaxis (PEP) and pre-emptive therapy (PET) for COVID-19. Methods: We will conduct two nested multicentre international double-blind randomized placebo-controlled clinical trials of hydroxychloroquine for: 1) PEP of asymptomatic household contacts or healthcare workers exposed to COVID-19 within the past four days, and 2) PET for symptomatic outpatients with COVID-19 showing symptoms for less than four days. We will recruit 1,500 patients each for the PEP and PET trials. Participants will be randomized 1:1 to receive five days of hydroxychloroquine or placebo. The primary PEP trial outcome will be the incidence of symptomatic COVID-19. The primary PET trial outcome will be an ordinal scale of disease severity (not hospitalized, hospitalized without intensive care, hospitalization with intensive care, or death). Participant screening, informed consent, and follow-up will be exclusively internet-based with appropriate regulatory and research ethics board approvals in Canada and the United States. Discussion: These complementary randomized-controlled trials are innovatively designed and adequately powered to rapidly answer urgent questions regarding the effectiveness of hydroxychloroquine to reduce virus transmission and disease severity of COVID-19 during a pandemic. In-person participant follow-up will not be conducted to facilitate social distancing strategies and reduce risks of exposure to study personnel. Innovative trial approaches are needed to urgently assess therapeutic options to mitigate the global impact of this pandemic. Trials registration: clinicaltrials.gov (NCT04308668); registered 16 March, 2020.
|Translated title of the contribution||Post-exposure prophylaxis or pre-emptive therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): study protocol for a pragmatic randomized-controlled trial|
|Number of pages||11|
|Journal||Canadian Journal of Anesthesia|
|State||Published - Sep 1 2020|
Bibliographical noteFunding Information:
American sponsor: David R. Boulware ; Canadian sponsor: Research Institute of the McGill University Health Centre ; American principal investigator: David R. Boulware ; Canadian principal investigators: Ryan Zarychanski , Todd C. Lee , Ilan Schwartz ; Trial design: David R. Boulware , Todd C. Lee , Kathy H. Hullsiek ; Research coordinators: Alyssa Agostinis , Nicole Marten , Zina Zaslawski ; Data collection: Ananta Bangdiwala , Emily G. McDonald , Matthew P. Cheng , Sarah Lofgren , Matt Pullen , Caleb Skipper , Katelyn A. Pastick ; Statistical analysis: Ananta Bangdiwala , Kathy Hullsiek , Nicole Engen ; Operational support: Sylvain A. Lother , Lauren J. MacKenzie , Alyssa Agostinis , Mahsa Abassi , Katelyn A. Pastick , Elizabeth C. Okafor , Matt Pullen , Lauren E. Kelly , Ananta Bangdiwala , David R. Boulware ; Protocol manuscript first draft: Sylvain A. Lother. Drs Emily G. McDonald and Todd C. Lee receive salary support from the Fonds de recherche du Qu?bec?Sant?. Dr. Cheng is a member of the scientific advisory board of GEn1E Lifesciences.?Ryan Zarychanski is the recipient of the Lyonel G Israsels Professorship in Hematology at the University of Manitoba. Dr. Turgeon is the Canada Research Chair in Critical Care Neurology and Trauma. Additional authors declare no conflicts of interest. Version 1.36, March 25 2020. U.S. Funding by Jan and David Baszucki, Alliance of Minnesota Chinese Organizations, Minnesota Chinese Chamber of Commerce, and University of Minnesota. Canadian funding by the Manitoba Medical Service Foundation. The funders will not contribute to the design of the study; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Purolator Canada provided in-kind courier support for the participating Canadian sites. This submission was handled by Dr. Gregory L. Bryson, Deputy Editor-in-Chief, Canadian Journal of Anesthesia.
Drs Emily G. McDonald and Todd C. Lee receive salary support from the Fonds de recherche du Québec—Santé. Dr. Cheng is a member of the scientific advisory board of GEn1E Lifesciences. Ryan Zarychanski is the recipient of the Lyonel G Israsels Professorship in Hematology at the University of Manitoba. Dr. Turgeon is the Canada Research Chair in Critical Care Neurology and Trauma. Additional authors declare no conflicts of interest.
© 2020, Canadian Anesthesiologists' Society.
- clinical trials
- healthcare worker
- post-exposure prophylaxis
- pre-emptive therapy
PubMed: MeSH publication types
- Clinical Trial Protocol
- Journal Article
- Multicenter Study
- Randomized Controlled Trial