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

Primary Purpose

Corona Virus Infection, SARS-CoV Infection, Coronavirus

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Hydroxychloroquine
Placebo oral tablet
Sponsored by
McGill University Health Centre/Research Institute of the McGill University Health Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corona Virus Infection focused on measuring COVID-19, SARS-COV-2, Coronavirus, Corona virus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Minnesota
  • University of Alberta
  • University of British Columbia
  • University of Manitoba
  • Eastern Health
  • McMaster University
  • Lawson Health Research Institute
  • Research Institute of the McGill University Health Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment

Placebo

Arm Description

Participants in this arm will receive the study drug, hydroxychloroquine.

Participants in this arm will receive a placebo treatment.

Outcomes

Primary Outcome Measures

Ordinal Scale of COVID19 Disease Severity at 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

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

Full Information

First Posted
June 5, 2020
Last Updated
April 5, 2022
Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators
University of Manitoba, University of Alberta, University of British Columbia, McMaster University, Lawson Health Research Institute, Eastern Health, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT04421664
Brief Title
Preemptive Therapy for SARS-Coronavirus-2 (COVID-19 PEP Canada)
Official Title
Preemptive Therapy for SARS-Coronavirus-2 (COVID-19 PEP Canada)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Terminated
Why Stopped
Request of Health Canada after publication of https://doi.org/10.7326/M20-4207
Study Start Date
March 25, 2020 (Actual)
Primary Completion Date
August 17, 2020 (Actual)
Study Completion Date
August 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators
University of Manitoba, University of Alberta, University of British Columbia, McMaster University, Lawson Health Research Institute, Eastern Health, University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection, SARS-CoV Infection, Coronavirus
Keywords
COVID-19, SARS-COV-2, Coronavirus, Corona virus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Participants in this arm will receive the study drug, hydroxychloroquine.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants in this arm will receive a placebo treatment.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Primary Outcome Measure Information:
Title
Ordinal Scale of COVID19 Disease Severity at 14 days
Description
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.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Incidence of Hospitalization
Description
Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Time Frame
14 days
Title
Incidence of COVID-19 related Death
Description
Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Time Frame
90 days
Title
Incidence of all-cause Death
Description
Outcome reported as the number of participants in each arm who expire due to all causes.
Time Frame
90 days
Title
Incidence of All-Cause Study Medicine Discontinuation or Withdrawal
Description
Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Time Frame
14 days
Title
Overall symptom severity at 5 and 14 days
Description
Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Time Frame
5 and 14 days
Title
Overall change in disease severity over 14 days among those who are symptomatic at baseline
Description
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)
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Todd C Lee, MD MPH FIDSA
Organizational Affiliation
Research Institute of the McGill University Health Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
University of Manitoba
City
Winnipeg
State/Province
Manitoba
Country
Canada
Facility Name
Eastern Health
City
Saint John's
State/Province
Newfoundland and Labrador
Country
Canada
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Lawson Health Research Institute
City
London
State/Province
Ontario
Country
Canada
Facility Name
Research Institute of the McGill University Health Centre
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4A3J1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified dataset will be included with publication.
IPD Sharing Time Frame
At time of publication
IPD Sharing Access Criteria
To be publicly provided
Citations:
PubMed Identifier
32383125
Citation
Lother SA, Abassi M, Agostinis A, Bangdiwala AS, Cheng MP, Drobot G, Engen N, Hullsiek KH, Kelly LE, Lee TC, Lofgren SM, MacKenzie LJ, Marten N, McDonald EG, Okafor EC, Pastick KA, Pullen MF, Rajasingham R, Schwartz I, Skipper CP, Turgeon AF, Zarychanski R, Boulware DR. 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. Can J Anaesth. 2020 Sep;67(9):1201-1211. doi: 10.1007/s12630-020-01684-7. Epub 2020 May 7.
Results Reference
background
PubMed Identifier
33204764
Citation
Lofgren SM, Nicol MR, Bangdiwala AS, Pastick KA, Okafor EC, Skipper CP, Pullen MF, Engen NW, Abassi M, Williams DA, Nascene AA, Axelrod ML, Lother SA, MacKenzie LJ, Drobot G, Marten N, Cheng MP, Zarychanski R, Schwartz IS, Silverman M, Chagla Z, Kelly LE, McDonald EG, Lee TC, Hullsiek KH, Boulware DR, Rajasingham R. Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19. Open Forum Infect Dis. 2020 Oct 19;7(11):ofaa500. doi: 10.1093/ofid/ofaa500. eCollection 2020 Nov.
Results Reference
background
PubMed Identifier
32673060
Citation
Skipper CP, Pastick KA, Engen NW, Bangdiwala AS, Abassi M, Lofgren SM, Williams DA, Okafor EC, Pullen MF, Nicol MR, Nascene AA, Hullsiek KH, Cheng MP, Luke D, Lother SA, MacKenzie LJ, Drobot G, Kelly LE, Schwartz IS, Zarychanski R, McDonald EG, Lee TC, Rajasingham R, Boulware DR. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial. Ann Intern Med. 2020 Oct 20;173(8):623-631. doi: 10.7326/M20-4207. Epub 2020 Jul 16. Erratum In: Ann Intern Med. 2021 Mar;174(3):435.
Results Reference
result
PubMed Identifier
32492293
Citation
Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, Skipper CP, Nascene AA, Nicol MR, Abassi M, Engen NW, Cheng MP, LaBar D, Lother SA, MacKenzie LJ, Drobot G, Marten N, Zarychanski R, Kelly LE, Schwartz IS, McDonald EG, Rajasingham R, Lee TC, Hullsiek KH. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. 2020 Aug 6;383(6):517-525. doi: 10.1056/NEJMoa2016638. Epub 2020 Jun 3.
Results Reference
result

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

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