Clinical trial NCT04421664: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Corona Virus Infection
SARS-CoV Infection
Coronavirus
Keywords: COVID-19
SARS-COV-2
Coronavirus
Corona virus
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: University of Manitoba
name: University of Alberta
name: University of British Columbia
name: McMaster University
name: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Eastern Health
name: University of Minnesota
First posted: 2020-06-09
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Ordinal Scale of COVID19 Disease Severity at 14 days
timeFrame: 14 days
Secondary outcomes:
measure: Incidence of Hospitalization
timeFrame: 14 days
measure: Incidence of COVID-19 related Death
timeFrame: 90 days
measure: Incidence of all-cause Death
timeFrame: 90 days
measure: Incidence of All-Cause Study Medicine Discontinuation or Withdrawal
timeFrame: 14 days
measure: Overall symptom severity at 5 and 14 days
timeFrame: 5 and 14 days
measure: Overall change in disease severity over 14 days among those who are symptomatic at baseline
timeFrame: 14 days
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Saint John's
country: Canada
facility: Eastern Health
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: London
country: Canada
facility: Lawson Health Research Institute
state: Ontario
city: Montréal
country: Canada
facility: Research Institute of the McGill University Health Centre
state: Quebec
Study officials:
affiliation: Research Institute of the McGill University Health Centre
name: Todd C Lee, MD MPH FIDSA
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.