Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine

Study Overview
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Brief Summary
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This is a double blind, placebo controlled study in approximately 2,000 health care workers at risk for being exposed to COVID-19. Eligible participants will be randomly assigned (1:1) to either treatment group (HCQ) or placebo in a double-blind fashion. Course of treatment is 30 days.

Detailed Description
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This is a double blind, placebo controlled study in approximately 2,000 health care workers at risk for being exposed to COVID-19. Eligible participants will be randomly assigned (1:1) to either treatment group (HCQ) or placebo in a double-blind fashion. After enrollment, baseline assessments will include nasopharyngeal swab for COVID-19 and a blood sample to detect seroconversion to COVID-19. For convenience, follow-up will be performed weekly through a direct to participant portal. A call center will provide support for any missed visits. Follow-up includes screening for any COVID-19 clinical infections, other respiratory infections, clinical events, adverse events, and Quality of Life (QoL) assessments. Course of treatment is 30 days. Participants are followed via survey weekly. At the end of treatment participants will return for repeat nasopharyngeal swab for COVID-19 and a blood sample to detect seroconversion to COVID-19. There will be one last contact at 8 weeks (2 months) from baseline.

Official Title
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Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine Trial (HERO-HCQ Trial)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion: Completed Informed Consent Age ≥ 18 years old Currently working in any environment in which there is a risk of exposure to patients with COVID-19 infections (healthcare worker) Exclusion Criteria: Prior diagnosis of COVID-19 infection Participation in another COVID-19 prophylaxis trial within 30 days of consent Respiratory illness with new-onset fever (Temperature > 100°F) or ongoing cough or dyspnea within 14 days Known allergy to HCQ or chloroquine Congenital prolonged QT syndrome Current or planned use of QT prolonging drugs (e.g. procainamide, disopyramide, mexiletine, flecainide, propafenone, amiodarone, sotalol, cimetidine, dronedarone, dofetilide, levofloxacin, ciprofloxacin, moxifloxacin) and other contraindicated medications End stage renal disease Pre-existing retinopathy Current or planned use of Hydroxychloroquine (study drug) for any indication Current or planned use of the following for treatment or prevention of COVID-19 infection: Chloroquine Azithromycin Known cirrhosis or severe liver disease History of severe skin reactions such as Steven-Johnson syndrome, toxic epidermal necrolysis History of psoriasis or porphyria Ventricular arrhythmias requiring medical treatment Severe coronary artery disease or heart failure/cardiomyopathy with ongoing symptoms Current or planned use of use of anti-seizure drugs History of Glucose-6-phosphate dehydrogenase deficiency

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
Interventional Model Description: Double blind, placebo-controlled, randomized clinical trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxychloroquine<br>Hydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30. | Drug: Hydroxychloroquine<br>* oral self administered tablet<br>* Other names: Plaquenil;|
| Placebo Comparator: Placebo<br>Matching placebo tablets | Drug: Placebo oral tablet<br>* oral self administered tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Infection With COVID-19 Infection | This measure was a combination of confirmed infection and suspected infection. Confirmed clinical infection was defined as new-onset of fever or cough or dyspnea AND confirmed COVID-19 positive test result via local PCRI testing. Suspected infection was defined as new-onset fever or cough or dyspnea without local PCR testing due to local restrictions and/or testing policies. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With COVID-19 Viral Shedding | Number of participants with COVID-19 infection shedding via Covance swab PCR testing | 30 days | 
| Number of Participants With Serious Adverse Events (SAEs) or Hydroxychloroquine-Associated Events of Special Interest (EOSIs) | Safety and Tolerability as determined by subject reported serious adverse events (SAEs) and hydroxychloroquine-associated events of special interest. EOSIs include: arrhythmias (ventricular), hepatic failure, bone marrow failure, aplastic anemia, prolonged QT interval, angioedema, dermatitis exfoliative, acute generalized exanthematous pustulosis, psychosis, suicidal ideation, seizure, methemoglobinemia. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydroxychloroquine, Coronavirus Infections, Novel Coronavirus, Protective agents, Prophylaxis, Chemoprophylaxis, Severe Acute Respiratory Syndrome, Respiratory Distress Syndrome, Adult, Acute Lung Injury, Virus Diseases, Lung Diseases, Respiratory Tract Diseases, Respiration Disorders, Lung Injury, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Respiratory Tract Infections, Antimalarials, Antiprotozoal Agents, Antiparasitic Agents, Anti-Infective Agents, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antirheumatic Agents, Chloroquine, Chloroquine diphosphate