Pre-exposure Prophylaxis for SARS-Coronavirus-2

Study Overview
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Brief Summary
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Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.

Detailed Description
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The current standard of care is observation and quarantine after exposure to COVID-19. There is no approved treatment or prophylaxis for COVID-19. As of March 6, 2020, the CDC estimates that the transmission of SARS-CoV2 after a U.S. household close contract is 10.5% (95%CI, 2.9 to 31.4%). Among all close contacts, the SARS-CoV2 transmission rate is estimated at 0.45% (95%CI, 0.12 to 1.6%) by the CDC. These estimates are based on monitoring of travel-associated COVID19 cases. Conversely, in a setting with community transmission, the secondary attack rate in China was 35% (95%CI, 27-44%) based on 48 transmissions among 137 persons in 9 index patients. Chloroquine or Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or reduce disease severity. It is not known at what dosing hydroxychloroquine may be effective for pre-exposure prophylaxis.

Official Title
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Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

Conditions
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COVID-19, Corona Virus Infection, ARDS, Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - A healthcare worker at high risk for COVID-19 exposure (defined below): Persons primarily working in emergency departments (physicians, nurses, ancillary staff, triage personnel) Persons primarily working in intensive care units (physicians, nurses, ancillary staff, respiratory therapists) Persons performing aerosol generating procedures (i.e. anesthesiologists, nurse anesthetists (CRNAs) First responders (i.e. EMTs, paramedics) Exclusion Criteria: Active COVID-19 disease Prior COVID-19 disease Current fever, cough, shortness of breath Allergy to chloroquine or hydroxychloroquine Prior retinal eye disease Known Chronic Kidney disease, Stage 4 or 5 or dialysis Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency Weight <40 kg Prolonged QT syndrome Current use of hydroxychloroquine, chloroquine, or cardiac medicines of flecainide, amiodarone, digoxin, procainamide, or propafenone Current use of medications with known significant drug-drug interactions: artemether, lumefantrine, mefloquine, tamoxifen, or methotrexate.

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Once Weekly<br>400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks | Drug: Hydroxychloroquine<br>* Hydroxychloroquine; 200mg tablet; oral<br>* Other names: Plaquenil;|
| Experimental: Intervention Twice Weekly<br>400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks | Drug: Hydroxychloroquine<br>* Hydroxychloroquine; 200mg tablet; oral<br>* Other names: Plaquenil;|
| Placebo Comparator: Control Group<br>Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks | Other: Placebo<br>* Placebo; tablet; oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19-free Survival | Outcome reported as the number of participants in each arm who are COVID-19-free at the end of study treatment. | up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Confirmed SARS-CoV-2 Detection | Outcome reported as the number of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment. | up to 12 weeks | 
| Incidence of Possible COVID-19 Symptoms | Outcome reported as the count of participants in each arm who report COVID-19-related symptoms during study treatment. | up to 12 weeks | 
| Incidence of All-cause Study Medicine Discontinuation | Outcome reported as the count of participants in each arm who discontinue study medication use for any reason during treatment. | up to 12 weeks | 
| Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End | Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity. | up to 12 weeks | 
| Incidence of Hospitalization for COVID-19 or Death | Outcome reported as the number of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment. | up to 12 weeks | 
| Incidence of Possible Study Medication-related Side Effects | Outcome reported as the number of participants in each arm who experience possible medication-related side effects during study treatment. | up to 12 weeks |