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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.
Lother, Sylvain A; Abassi, Mahsa; Agostinis, Alyssa; Bangdiwala, Ananta S; Cheng, Matthew P; Drobot, Glen; Engen, Nicole; Hullsiek, Kathy H; Kelly, Lauren E; Lee, Todd C; Lofgren, Sarah M; MacKenzie, Lauren J; Marten, Nicole; McDonald, Emily G; Okafor, Elizabeth C; Pastick, Katelyn A; Pullen, Matthew F; Rajasingham, Radha; Schwartz, Ilan; Skipper, Caleb P; Turgeon, Alexis F; Zarychanski, Ryan; Boulware, David R.
  • Lother SA; Department of Internal Medicine, Section of Critical Care, University of Manitoba, Winnipeg, MB, Canada. slother@manitoba-physicians.ca.
  • Abassi M; Section of Infectious Diseases, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada. slother@manitoba-physicians.ca.
  • Agostinis A; Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Bangdiwala AS; Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
  • Cheng MP; School of Medicine, Trinity College Dublin, Dublin, Ireland.
  • Drobot G; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
  • Engen N; Divisions of Infectious Diseases & Medical Microbiology, McGill University Health Centre, Montreal, QC, Canada.
  • Hullsiek KH; McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, QC, Canada.
  • Kelly LE; Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.
  • Lee TC; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
  • Lofgren SM; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
  • MacKenzie LJ; Department of Pediatrics and Child Health, Department of Pharmacology, University of Manitoba, Winnipeg, MB, Canada.
  • Marten N; Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, QC, Canada.
  • McDonald EG; Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Okafor EC; Section of Infectious Diseases, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
  • Pastick KA; Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
  • Pullen MF; Critical Care Research, St-Boniface Hospital, Winnipeg, MB, Canada.
  • Rajasingham R; Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, QC, Canada.
  • Schwartz I; Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Skipper CP; Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Turgeon AF; Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Zarychanski R; Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Boulware DR; Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Can J Anaesth ; 67(9): 1201-1211, 2020 09.
Article in English | MEDLINE | ID: covidwho-275845
Semantic information from SemMedBD (by NLM)
1. 2019 novel coronavirus CAUSES Disease
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Disease
2. Post-Exposure Prophylaxis USES hydroxychloroquine
Subject
Post-Exposure Prophylaxis
Predicate
USES
Object
hydroxychloroquine
3. Symptoms PROCESS_OF Outpatients
Subject
Symptoms
Predicate
PROCESS_OF
Object
Outpatients
4. hydroxychloroquine DISRUPTS viral transmission
Subject
hydroxychloroquine
Predicate
DISRUPTS
Object
viral transmission
5. 2019 novel coronavirus CAUSES Disease
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Disease
6. Post-Exposure Prophylaxis USES hydroxychloroquine
Subject
Post-Exposure Prophylaxis
Predicate
USES
Object
hydroxychloroquine
7. Symptoms PROCESS_OF Outpatients
Subject
Symptoms
Predicate
PROCESS_OF
Object
Outpatients
8. hydroxychloroquine DISRUPTS viral transmission
Subject
hydroxychloroquine
Predicate
DISRUPTS
Object
viral transmission
ABSTRACT

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 11 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.
RéSUMé CONTEXTE Le syndrome respiratoire aigu sévère du coronavirus 2 (SARS-CoV-2) est apparu en décembre 2019, provoquant la pandémie de la COVID-19. À l'heure actuelle, il n'existe aucun traitement fondé sur des données probantes permettant de prévenir la COVID-19 suite à une exposition au virus ou de prévenir l'aggravation des symptômes suite à une infection confirmée. Nous décrivons la conception d'une étude clinique examinant l'utilisation d'hydroxychloroquine en tant que prophylaxie post-exposition (PPE) et de traitement préventif (TP) pour la COVID-19. MéTHODE Nous réaliserons deux études cliniques imbriquées contrôlées par placebo, randomisées, à double insu, internationales et multicentriques examinant l'utilisation d'hydroxychloroquine pour  1) la prophylaxie post-exposition des contacts asymptomatiques dans un même foyer ou les travailleurs de la santé exposés à la COVID-19 au cours des quatre derniers jours, et 2) le traitement préventif des patients symptomatiques en ambulatoire atteints de COVID-19 et présentant des symptômes pour une durée totale de moins de quatre jours. Nous recruterons 1500 patients pour chaque bras de l'étude (PPE et TP). Les participants seront randomisés à un ratio de 1  1 pour recevoir cinq jours d'hydroxychloroquine ou de placebo. Le critère d'évaluation principal de l'étude PPE sera l'incidence de COVID-19 symptomatique. Le critère d'évaluation principal de l'étude TP consistera en une échelle ordinale de la gravité de la maladie (pas d'hospitalisation, hospitalisation sans soins intensifs, hospitalisation avec soins intensifs, ou décès). La sélection des participants, le consentement éclairé et le suivi se feront exclusivement en ligne après avoir obtenu les consentements réglementaires et des comités d'éthique de la recherche appropriés au Canada et aux États-Unis.

DISCUSSION:

Ces études randomisées contrôlées complémentaires sont conçues de façon innovatrice et disposent de la puissance nécessaire pour répondre rapidement aux questions urgentes quant à l'efficacité de l'hydroxychloroquine pour réduire la transmission et la gravité de la maladie de la COVID-19 pendant une pandémie. Le suivi des participants ne sera pas réalisé en personne afin de faciliter les stratégies de distanciation sociale et de réduire le risque d'exposition du personnel de l'étude. Des approches innovatrices d'études sont nécessaires afin d'évaluer rapidement les options thérapeutiques pour mitiger l'impact global de cette pandémie. ENREGISTREMENT DE L'éTUDE clinicaltrials.gov (NCT04308668); enregistrées le 16 mars 2020.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Post-Exposure Prophylaxis / Pandemics / Hydroxychloroquine Type of study: Controlled clinical trial / Clinical Practice Guide / Randomized controlled trials Limits: Humans Language: English Journal: Can J Anaesth Journal subject: Anesthesiology Year: 2020 Document Type: Article Affiliation country: S12630-020-01684-7

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Post-Exposure Prophylaxis / Pandemics / Hydroxychloroquine Type of study: Controlled clinical trial / Clinical Practice Guide / Randomized controlled trials Limits: Humans Language: English Journal: Can J Anaesth Journal subject: Anesthesiology Year: 2020 Document Type: Article Affiliation country: S12630-020-01684-7