Clinical trial NCT04308668: Post-exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2
Official title: Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Corona Virus Infection
Acute Respiratory Distress Syndrome
SARS-CoV Infection
Coronavirus
Coronavirus Infections
Keywords: COVID-19
Corona Virus
SARS-COV-2
Coronavirus
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: University of Manitoba
name: University of Alberta
First posted: 2020-03-16
Enrollment: 1312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Asymptomatic participants are randomized and analyzed separate from symptomatic participants.
Primary purpose: TREATMENT

Brief summary: Study Objective:

1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus.
2. 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. The current strategy uses a public health model of identifying infected cases, isolation, and quarantine to stop transmission. Once exposed, observation is standard-of-care. Therapy is generally not given to persons who are not hospitalized. The doses of hydroxychloroquine being used are within the normal standard FDA-approved doses.

Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or early preemptive therapy may decrease disease severity. This trial will use a modification of standard malaria dosing of hydroxychloroquine to provide post-exposure prophylaxis to prevent disease or preemptive therapy for those with early symptoms. People around the the United States and Canada can participate to help answer this critically important question. No in-person visits are needed.

This trial is targeting 5 groups of people NATIONWIDE to participate:

1. If you are symptomatic with a positive COVID-19 test within the first 4 days of symptoms and are not hospitalized; OR
2. If you live with someone who has been diagnosed with COVID-19, with your last exposure within the last 4 days, and do not have any symptoms; OR
3. If you live with someone who has been diagnosed with COVID-19, and your symptoms started within the last 4 days; OR
4. If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 4 days and do not have symptoms; OR
5. If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 4 days AND have compatible symptoms starting within the last 4 days;

You may participate if you live anywhere in the United States (including territories) or in the Canadian Provinces of Quebec, Manitoba, Alberta, or Ontario.

For information on how to participate in the research trial, go to covidpep.umn.edu or email covid19@umn.edu for instructions. Please check your spam folder if you email.

In Canada, for trial information, please go to: www.covid-19research.ca

Eligibility criteria: Inclusion Criteria:

* Provision of informed consent
* Exposure to a COVID19 case within 4 days as either a household contact or occupational exposure, OR
* Symptomatic COVID19 case with confirmed diagnosis within 4 days of symptom onset OR symptomatic high risk exposure with known COVID19 contact and within 4 days of symptom onset;

Exclusion Criteria:

* Current hospitalization
* Allergy to hydroxychloroquine
* Retinal eye disease
* Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency
* Known chronic kidney disease, stage 4 or 5 or receiving dialysis
* Structural or ischemic heart disease
* Personal or Family History of Prolonged QT syndrome
* Weight \< 50 kg
* Known Porphyria
* Current use of: hydroxychloroquine or cardiac medicines of: flecainide, Tambocor; amiodarone, Cordarone, Pacerone; digoxin or Digox, Digitek, Lanoxin; procainamide or Procan, Procanbid, propafenone, Rythmal, sotalol;
* Current use of medicines which prolong the QT interval including:

  * Antimicrobials: levofloxacin, ciprofloxacin, moxifloxacin, azithromycin, clarithromycin, erythromycin, ketoconazole, itraconazole, or mefloquine
  * Antidepressants: amitriptyline, citalopram, desipramine, escitalopram, imipramine, doxepin, fluoxetine, wellbutrin, or venlafaxine
  * Antipsychotic or mood stabilizers: haloperidol, droperidol, lithium, quetiapine, thioridazine, ziprasidone
  * Methadone
  * Sumatriptan, zolmitriptan

Primary outcomes:
measure: Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline
timeFrame: 14 days
measure: Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline
timeFrame: baseline and 14 days
Secondary outcomes:
measure: Rate of Hospitalization
timeFrame: 14 days
measure: Rate of Death
timeFrame: Approximately 30 days
measure: Rate of Confirmed SARS-CoV-2 Detection
timeFrame: 14 days
measure: Occurrence of Symptoms Compatible With COVID-19 (Possible Disease)
timeFrame: 14 days
measure: Rate 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: Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry
timeFrame: 14 days
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Nationwide Enrollment via Internet, please email: covid19@umn.edu
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Montréal
country: Canada
facility: Research Institute of the McGill University Heath Centre
state: Quebec
Study officials:
affiliation: University of Minnesota
name: David Boulware, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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.
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