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

Corona Virus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04421664
• Other study ID #: 2020-6549
• Status: Terminated
• Phase: Phase 3
• Start date: March 25, 2020
• Est. completion date: August 17, 2020

Study information

• Verified date: April 2022
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 70
• Est. completion date: August 17, 2020
• Est. primary completion date: August 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Corona Virus Infection
• Coronavirus
• Coronavirus Infections
• COVID-19
• Infections
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Drug:
• Hydroxychloroquine
200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days
• Placebo oral tablet
4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	Lawson Health Research Institute	London	Ontario
Canada	Research Institute of the McGill University Health Centre	Montréal	Quebec
Canada	Eastern Health	Saint John's	Newfoundland and Labrador
Canada	University of British Columbia	Vancouver	British Columbia
Canada	University of Manitoba	Winnipeg	Manitoba
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (8)

Lead Sponsor	Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre	Eastern Health, Lawson Health Research Institute, McMaster University, University of Alberta, University of British Columbia, University of Manitoba, University of Minnesota

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

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 — View 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. — View 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. — View 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, Ra — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	14 days
Secondary	Incidence of Hospitalization	Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.	14 days
Secondary	Incidence of COVID-19 related Death	Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.	90 days
Secondary	Incidence of all-cause Death	Outcome reported as the number of participants in each arm who expire due to all causes.	90 days
Secondary	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.	14 days
Secondary	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)	5 and 14 days
Secondary	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)	14 days