Hydroxychloroquine to Prevent COVID-19 Disease Amongst Healthcare Workers

Study Overview
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Brief Summary
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The objectives of PROVIDE are to: Determine if prophylactic once weekly hydroxychloroquine reduces the incidence of conversion from SARS-2-CoVnasopharyngeal swab negative to positive To determine if weekly prophylactic hydroxychloroquine reduced the severity of COVID-19 symptoms To determine the safety of taking weekly prophylactic hydroxychloroquine

Official Title
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Hydroxychloroquine to Prevent COVID-19 Disease Amongst Healthcare Workers (PROVIDE): A Parallel Randomized Controlled Trial

Conditions
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Corona Virus Infection

Intervention / Treatment
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* Drug: Apo-Hydroxychloroquine
* Drug: Matched Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older to participate. Healthcare workers with primary practice in intensive care unit, general internal medicine, COVID-19 testing centres, emergency rooms, and nursing homes. COVID_19 symptom free at the time of randomization and have a negative diagnostic swab. Exclusion Criteria: Known COVID-19 positivity defined as: a laboratory confirmed case as defined by the local public health institutes Suspected COVID-19 positivity defined as possessing symptoms consistent with COVID-19 infections such as: headache, fever, nausea, vomiting, diarrhea, dyspnea, dry cough Healthcare workers with pre-existing retinopathy or serious visual problems Healthcare workers with known malignancies receiving active chemotherapy or immune modifying medications Healthcare workers with known autoimmune disorders Healthcare workers with known QT prolongation History of ventricular arrhythmias Participants at risk of malignant arrythmias ○ At risk defined as: A sudden loss of consciousness with injury; anyone in their immediate family, under the age of 45year, with sudden cardiac death; anyone family history of long QT syndrome Known sensitivity/allergy to hydroxychloroquine Healthcare workers that are currently pregnant Healthcare workers that are already taking chloroquine or hydroxychloroquine Healthcare workers on colchicine or any other anti-viral medication Healthcare workers taking a medication that may interact with hydroxychloroquine (see table below Inability to take oral medications Inability to provide written consent Known G6PD 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: Parallel two-armed, multi-centred, blinded, stratified, superiority, randomized controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention - Hydroxychloroquine<br> | Drug: Apo-Hydroxychloroquine<br>* Hydroxychloroquine sulfate 400mg PO BID on day one, then 400mg PO weekly, to be taken with meals for two months total.<br>|
| Placebo Comparator: Control<br> | Drug: Matched Placebo<br>* Matching Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive for SARS-CoV-2 | The number of HCW that tested positive for SARS-CoV-2 | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital admissions | The number of HCW that required hospital admission secondary to SARS-CoV-2 | at any time after first dose to hospital discharge, truncated at 60 days | 
| Intensive care unit admissions | The number of HCW that required intensive care unit admission | at any time after first dose to hospital discharge, truncated at 60 days | 
| Intubation and mechanical ventilation | The number of HCW that required intubation and mechanical ventilation | at any time after first dose, truncated at 60 days | 
| ICU length of stay | number of days admitted to the ICU | from randomization to hospital discharge, truncated at 60 days | 
| Hospital length of stay | number of days admitted to the hospital | from randomization to hospital discharge, truncated at 60 days | 
| Mortality | Death | from randomization to 60 days | 
| Incidence of adverse events | Gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting), Hypoglycemia, Abdominal LFTs, Angioedema, Opthalmic (corneal changes, decreased visual acuity, macular degeneration, retinal changes), Bronchospasm | from randomization to 60 days |