Post-exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2

Phase 3

Completed

Conditions: Corona Virus Infection
Coronavirus Infections
Acute Respiratory Distress Syndrome
Coronavirus
SARS-CoV Infection

Interventions: Drug: Hydroxychloroquine
Other: Placebo

Registration Number: NCT04308668

Lead Sponsor: University of Minnesota

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1312

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline	baseline and 14 days	Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline	14 days	Number of participants at 14 days post enrollment with active COVID19 disease among those who were asymptomatic at baseline.

Secondary Outcome Measures

Name	Time	Method
Rate of Hospitalization	14 days	Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Rate of Death	Approximately 30 days	Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease through study completion of 14 days. For those hospitalized within the 14-day study period, the protocol specified follow up would occur for up to 90 days to capture the final outcome of participants' hospitalization. Approximately 30-days was the maximal follow up for hospitalization outcome needed in the trial.
Rate of Confirmed SARS-CoV-2 Detection	14 days	Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Occurrence of Symptoms Compatible With COVID-19 (Possible Disease)	14 days	Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID-19 infection.
Rate 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 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)
Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry	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 number of participants who report a score of 3.

Trial Locations

Locations (5): Research Institute of the McGill University Heath Centre
🇨🇦
Montréal, Quebec, Canada
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Nationwide Enrollment via Internet, please email: covid19@umn.edu
🇺🇸
Minneapolis, Minnesota, United States
University of Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
University of Alberta
🇨🇦
Edmonton, Alberta, Canada