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

Study Overview
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Brief Summary
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Study Objective: To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 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
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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: If you are symptomatic with a positive COVID-19 test within the first 4 days of symptoms and are not hospitalized; OR 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 If you live with someone who has been diagnosed with COVID-19, and your symptoms started within the last 4 days; OR 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 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

Official Title
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Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

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

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Asymptomatic participants are randomized and analyzed separate from symptomatic participants.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Participants in this arm will receive the study drug. | Drug: Hydroxychloroquine<br>* 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days<br>* Other names: Plaquenil;|
| Placebo Comparator: Placebo<br>Participants in this arm will receive a placebo treatment. | Other: Placebo<br>* 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Hospitalization | Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease. | 14 days | 
| Rate of Death | 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. | Approximately 30 days | 
| Rate of Confirmed SARS-CoV-2 Detection | Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection. | 14 days | 
| Occurrence of Symptoms Compatible With COVID-19 (Possible Disease) | Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID-19 infection. | 14 days | 
| Rate 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 | 
| 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 | 
| Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry | 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. | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Corona Virus, SARS-COV-2, Coronavirus