Preemptive Therapy for SARS-Coronavirus-2 (COVID-19 PEP Canada)

Phase 3

Terminated

• Conditions: Corona Virus Infection; SARS-CoV Infection; Coronavirus
• Interventions: Drug: Placebo oral tablet; Drug: Hydroxychloroquine

• Registration Number: NCT04421664
• Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary

Study Objective:

To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.

Detailed Description

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing COVID19. Therapy is generally not given to persons who are not hospitalized.

Hydroxychloroquine may have antiviral effects against SARS-CoV2 which may decrease disease severity when given early. This trial will use a modification of standard malaria dosing of hydroxychloroquine to provide preemptive therapy for those with early symptoms.

This study is a continuation of NCT04308668 which looked at post-exposure prophylaxis (now closed) and early treatment in the USA (now closed, data to be pooled) and Canada (which continues in this study). On April 28, 2020 NCT04308668 changed its primary outcome to symptomatic improvement in the preemptive therapy arm. This study continues enrollment for the primary ordinal outcome of hospitalization; hospitalization with intensive care stay; or death.

People in the participating Canadian provinces can help answer this critically important question. No in-person visits are needed.

The doses of hydroxychloroquine being used have been approved by Health Canada.

This trial is targeting the following groups of people:

If you are symptomatic with a positive COVID-19 test within the first 4 days of symptoms and are not hospitalized; OR If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 14 days AND have compatible symptoms starting within the last 4 days;

You may participate if you live anywhere in the Canadian Provinces of Quebec, Manitoba, Alberta, British Columbia, Newfoundland or Ontario.

For information on how to participate in the research trial, go to:

www.covid-19research.ca

Study Timeline

• Study Start: 2020-03-25
• Study First Submitted: 2020-06-05
• Study First Submitted QC: 2020-06-05
• Study First Posted: 2020-06-09
• Primary Completion: 2020-08-17
• Study Completion: 2020-08-17
• Status Verified: 2022-04
• Last Update Submitted: 2024-10-09
• Last Update Posted: 2024-10-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Age 18 years of age or older AND provision of informed consent

WITH

Symptomatic COVID-19 disease with confirmed diagnosis with PCR+ SARS-CoV-2 within <= 4 days of symptoms

OR

Healthcare worker with compatible symptoms with exposure to known PCR+ case <= 14 days (and no available/pending testing for the individual).

Exclusion Criteria

• Current hospitalization
• Allergy to chloroquine or hydroxychloroquine
• Severe diarrhea and/or vomiting
• Significant hepatic impairment defined as known cirrhosis with history of hepatic encephalopathy or ascites.
• Prior retinal eye disease
• Concurrent malignancy requiring chemotherapy
• Known Chronic Kidney disease, Stage 4 or 5 or dialysis.
• Known glucose-6 phosphate dehydrogenase (G6PD) deficiency.
• Known ventricular arrythmia, known prolonged QTc interval, or any known episode of sudden cardiac death
• Known Porphyria
• Weight <40 kg
• Known Pregnancy of Breastfeeding
• Current use of chloroquine or hydroxychloroquine
• Current use of Artemether, Dapsone, Lumefantrine or Mefloquine
• Current use of Cardiac medicines: amiodarone, digoxin, dofetilide, flecainide, procainamide, sotalol, or propafenone
• Current use of the following antimicrobials: levofloxacin, ciprofloxacin, moxifloxacin, azithromycin, clarithromycin, erythromycin, ketoconazole, or itraconazole
• Current use of the following antidepressants: amitriptyline, citalopram, desipramine, escitalopram, imipramine, doxepin, fluoxetine, sertraline, bupropion (Wellbutrin), or venlafaxine
• Current use of the following antipsychotic or mood stabilizers: haloperidol, droperidol, lithium, quetiapine, thioridazine, ziprasidone
• Current use of methadone
• Current use of Sumatriptan, Zolmitriptan other than "as needed"
• Current use of systemic chemotherapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo oral tablet	Participants in this arm will receive a placebo treatment.
Treatment	Hydroxychloroquine	Participants in this arm will receive the study drug, hydroxychloroquine.

Primary Outcome Measures

Name	Time	Method
Ordinal Scale of COVID19 Disease Severity at 14 days	14 days	Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.

Secondary Outcome Measures

Name	Time	Method
Incidence of All-Cause Study Medicine Discontinuation or Withdrawal	14 days	Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Overall change in disease severity over 14 days among those who are symptomatic at baseline	14 days	Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Incidence of Hospitalization	14 days	Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Incidence of COVID-19 related Death	90 days	Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Incidence of all-cause Death	90 days	Outcome reported as the number of participants in each arm who expire due to all causes.
Overall symptom severity at 5 and 14 days	5 and 14 days	Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

Trial Locations

Locations (8)

McMaster University; 🇨🇦 Hamilton, Ontario, Canada

Research Institute of the McGill University Health Centre; 🇨🇦 Montréal, Quebec, Canada

University of Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

Eastern Health; 🇨🇦 Saint John's, Newfoundland and Labrador, Canada

University of British Columbia; 🇨🇦 Vancouver, British Columbia, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Lawson Health Research Institute; 🇨🇦 London, Ontario, Canada

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States