Hydroxychloroquine as Post-Exposure Prophylaxis Against COVID-19 Infection

Study Overview
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Brief Summary
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This is a prospective, double-blind, randomized, placebo-controlled study in two distinct cohorts to evaluate the efficacy and safety of hydroxychloroquine in the prevention of COVID-19 infection.

Official Title
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Randomized, Double-Blind, Controlled Trial of Hydroxychloroquine vs Placebo as Post-Exposure Prophylaxis Against COVID-19 Infection

Conditions
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COVID-19, SARS-CoV 2

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria Cohort A: ≥ 18 years old Employee of healthcare organization in South Dakota or Sanford Health employee in any location and with exposure to a person with COVID-19 within the last 5 days Occupational exposure as determined by the participant's employee health department (i.e. not wearing the proper Personal Protective Equipment (PPE)) Criteria according to Center for Disease Control (CDC) guidelines Community exposure (within 6 feet for at least 15 minutes) No current symptoms attributable to COVID-19, per HCW report (fever, cough, difficulty breathing, sore throat) No prior COVID-19 positive diagnosis (eligible if previous testing is negative and meets all other inclusion and exclusion) Ability to provide informed consent Inclusion Criteria - Cohort B ≥ 18 years old High-risk person who had close contact (i.e. within 6 feet for at least 15 minutes) with a COVID-19 positive person within the last 5 days and is a South Dakota resident or high-risk person with close household contact of a COVID-19 positive Sanford employee High-risk person defined by: Age 18-44 with 2 or more comorbidities listed below Age 45-79 with any comorbid condition listed below Age 80 and above (regardless of comorbid conditions) Co-morbid list Congestive Heart Failure (CHF) Chronic lung disease (Includes any of the following: asthma, chronic obstructive pulmonary disease, emphysema) Solid organ transplant or immunosuppression (Defined as an outpatient prescription of greater than 10 mg/day of prednisone or equivalent, use of chemotherapy, or use of immunosuppressive agents for solid organ transplant or for an autoimmune disease.) Chronic Kidney Disease or End Stage Renal Disease Diabetes mellitus Cardiovascular disease/Hypertension Smoking/Vaping (currently using or history of using in the past 1 year) Obesity (calculated by height and weight per participant report) Hyperlipidemia No current symptoms attributable to COVID-19 No prior COVID-19 positive diagnosis (eligible if previous testing is negative and meets all other inclusion and exclusion) Ability to provide informed consent Confirmed review of concomitant medications (with emphasis on cardiac medications) Exclusion Criteria Cohort A & B: Known allergy to hydroxychloroquine or quinine Known history of long QT syndrome Known history of arrhythmia or dysrhythmia Known current QTc >500 ms Known G6PD deficiency Known history of hypoglycemia Pregnant or Nursing by patient history Use of any of the following concomitant medications: See Appendix D for Exclusion medication list Concurrent diagnosis of dermatitis, porphyria, or psoriasis History of chronic liver disease, including cirrhosis and/or diagnosis of hepatitis (infectious, idiopathic, or immune) History of chronic kidney disease Pre-existing retinopathy Already taking hydroxychloroquine Any condition or medication in the opinion of the investigator that would prohibit the use of hydroxychloroquine Enrollment in another clinical with investigational drug or device Inability to swallow pills Adults unable to provide informed consent

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Healthcare worker (hydroxychloroquine)<br> | Drug: Hydroxychloroquine<br>* Participants randomized to hydroxychloroquine will take 800mg on day 1 followed by 400mg on days 2-5.<br>|
| Placebo Comparator: Cohort A: Healthcare worker (placebo)<br> | Dietary Supplement: Vitamin D<br>* Participants randomized to placebo will take IU1600 on day 1 and IU 800 on days 2-5.<br>|
| Experimental: Cohort B: High-Risk participant (hydroxychloroqine)<br> | Drug: Hydroxychloroquine<br>* Participants randomized to hydroxychloroquine will take 800mg on day 1 followed by 400mg on days 2-5.<br>|
| Placebo Comparator: Cohort B: High-Risk participant (placebo)<br> | Dietary Supplement: Vitamin D<br>* Participants randomized to placebo will take IU1600 on day 1 and IU 800 on days 2-5.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Percentage of COVID-19 Exposed Healthcare Workers Treated With Hydroxychloroquine With a Positive COVID-19 Test. | Determine whether post-exposure prophylaxis with hydroxychloroquine can prevent COVID-19 in healthcare workers who have been exposed to a known case of COVID-19. | At enrollment completion outcome 1 will be analyzed. | 
| Cohort B: Percentage of COVID-19 Exposed High-risk Individuals Treated With Hydroxychloroquine With a Positive COVID-19 Test. | Determine whether post-exposure prophylaxis with hydroxychloroquine can prevent COVID-19 in high-risk individuals who have been exposed to a known case of COVID-19. | At enrollment completion outcome 2 will be analyzed. |