Hydroxychloroquine Use in Hospitalized Patients With COVID-19: Impact on Progression to Severe or Critical Disease

Study Overview
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Brief Summary
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The primary objective is to assess the impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease.

Detailed Description
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This study will utilize a randomized, placebo-controlled, double-blinded design. Patients admitted with confirmed COVID-19, and at least 1 of the following: requiring oxygen supplementation (≤4 liters of oxygen via nasal cannula or increase from baseline), bilateral infiltrates on CT/CXR, age >65, diabetes, hypertension, BMI > 35, chronic lung disease, cardiovascular disease, chronic kidney disease, cancer (hematologic malignancies, lung cancer, and metastatic disease), will be randomized in a 1:1 fashion to hydroxychloroquine 400 mg PO BID x 2 doses, then 200 mg PO BID x 8 doses or placebo at a matching schedule.

Official Title
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Hydroxychloroquine Use in Hospitalized Patients With COVID-19: Impact on Progression to Severe or Critical Disease

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to Wellstar Kennestone Hospital Age 18 years or older Laboratory-confirmed COVID-19 At least 1 of the following: Requiring oxygen supplementation at ≤ 4 liters via nasal cannula or increase from baseline Bilateral infiltrates on CXR or CT of chest Age 65 or older Diabetes Hypertension BMI > 35 Chronic lung disease Cardiovascular disease Chronic kidney disease Cancer (hematologic malignancies, lung cancer, and metastatic disease) Exclusion Criteria: Unable to provide informed consent Unable to take oral medication Severe/critical COVID-19 disease at presentation Intensive care or intermediate care required at admission or within 48 hours Requiring oxygen supplementation via high flow nasal cannula, bipap, or non-rebreather mask at admission or within 48 hours Likelihood of survival <48 hours in the opinion of the primary physician or transitioned to comfort measures within 48 hours of admission Inability to take hydroxychloroquine due to allergy, QTc > 500 ms (male) or 520 ms (female) prior to initiation of hydroxychloroquine, pre-existing retinopathy, known G6PD deficiency, known porphyria, or significant drug- drug interactions Pregnant or breastfeeding Severe liver disease (Child-Pugh Class C)

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br> | Drug: Hydroxychloroquine<br>* Hydroxychloroquine 400 mg PO BID x 2 doses, then 200 mg PO BID x 8 doses<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo 400 mg PO BID x 2 doses, then 200 mg PO BID x 8 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease. | The impact will be evaluated by comparing rates of a composite primary outcome in patients randomized to hydroxychloroquine versus those randomized to placebo. The composite outcome includes progression to severe/critical disease or death (including withdrawal of care/hospice transfer). Progression to severe/critical disease is defined by requiring oxygen delivery via high flow nasal cannula, non-rebreather mask, bipap, or transfer to intensive care (ICU) or intermediate care units (IMCU) due to COVID-19-related complications. | 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital length of stay |  | 30 Days | 
| 30-Day Mortality |  | 30 Days | 
| Resolution of Symptoms | Resolution of symptoms will be assessed using standard medical interview procedures with the subject and review of the medical records. | 14 Days | 
| Incidence of QTc >500ms after initiation of therapy |  | 30 Days | 
| Incidence of discontinuation of therapy |  | 30 Days |