Hydroxychloroquine With or Without Azithromycin for Virologic Cure of COVID-19

Study Overview
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Brief Summary
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Q-PROTECT is a placebo controlled randomized trial (RCT) to ascertain the efficacy of hydroxychloroquine (HC) alone or, in combination with azithromycin (AZ), in reducing viral load in patients with COVID 19.

Detailed Description
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Reducing viral load is potentially key to reducing viral transmission between humans. Observational data suggests HC and AZ may reduce the viral load. In this study we will randomise ambulatory patients with Covid 19 (confirmed by PCR in combination with clinical symptoms) to receive HC/AZ or HC/placebo or placebo for 7 days. On days 2-14, participants will be reviewed by a member of the research team and samples will be obtained for viral load, an ECG recorded and physical examination performed. On days 15-20, participants will be reviewed by telephone using a semi structured questionnaire. On day 21 participants will be examined in person and an oronasopharyngeal swabs obtained for PCR analysis. Participants will be followed for 6 months via their medical records.

Official Title
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Randomized Placebo-controlled Trial of Hydroxychloroquine With or Without Azithromycin for Virologic Cure of COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Azithromycin
* Other: Placebo Tablet
* Other: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is in HMC facility for low-acuity, Covid-positive patients being quarantined. Positive Covid test on qualitative assay used during routine care (i.e. not as part of Q-PROTECT) Age at least 18 Exclusion Criteria: Treating physician judges patient not appropriate for study participation for any reason Age <18 Breastfeeding or pregnancy (patient-reported pregnancy status is sufficient) Hypersensitivity to chloroquine or HC or AZ History of or known QT prolongation EKG required before study entry and on each visit during the subject's first seven days on pro-tocol, during the time period HC is being taken Baseline QTc >480 if QRS width normal; QTc >510 if QRS >120 Known G6PD deficiency, porphyria, or retinopathy (eye exam prior to study entry) Known hepatic or renal disease (or abnormality on liver or renal function testing at study day 1) Low magnesium or low potassium (by testing on day 1) Current (pre-study) therapy with antimalarial or dapsone Current (pre-study) therapy with antiviral agents (e.g. oseltamivir) Tisdale36 score exceeding 6 as tallied below (based on ACC recommendations)* 1 point each: age>67, female sex, or being on loop diuretic 2 points each: serum potassium <3.6, QTc>449, acute myocardial infarction 3 points each: sepsis, heart failure, QT-prolonging drugs

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: Combination therapy group<br>hydroxychloroquine 200mg TID for 7 days plus Azithromycin 500mg OD 1st day and 250 from day 2 to 5 | Drug: Hydroxychloroquine<br>* Hydroxychloroquine 200 mg tablet oral, one tablet three times a day for 7 days<br>* Other names: Plaquenil,;Drug: Azithromycin<br>* Azithromycin 250 mg capsules oral, 2 capsules on day one, followed by 1 capsule once a day for days 2-5.<br>* Other names: Zithromax, Azithrocin;|
| Active Comparator: Monotherapy therapy group<br>hydroxychloroquine 200mg TID for 7 days plus Placebo 1 tab OD 1st day and 1 tab from day 2 to 5 | Drug: Hydroxychloroquine<br>* Hydroxychloroquine 200 mg tablet oral, one tablet three times a day for 7 days<br>* Other names: Plaquenil,;Other: Placebo capsules<br>* Oral 2 capsules on day one, followed by 1 capsule once a day for days 2-5.<br>|
| Placebo Comparator: Control group<br>Placebo Cap TID for 7 days plus Placebo 1 tab OD 1st day and 1 tab from day 2 to 5 | Other: Placebo Tablet<br>* Oral, one tablet three times a day for 7 days<br>Other: Placebo capsules<br>* Oral 2 capsules on day one, followed by 1 capsule once a day for days 2-5.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of virologically cured (PCR-negative status) as assessed on day six | Days | Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| virologic cure on other study days | Days | Day14 and Day 21 | 
| virologic semiquantitative analysis of changing viral load | Days | Day 1 to Day 21 | 
| proportion of initially symtomatic subjects with disappearance of clinical symptoms | Days | Day14 and Day 21 | 
| proportion of initially asymtomatic subjects with appearance of new clinical symptoms | Days | Day14 and Day 21 | 
| proportions of subjects with potentially medication- related adverse events | grades | 7 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid19, Qatar, Coronavirus, Hydroxychloroquine, Respiratory disease, Pandemic, Azithromycin, Viral Load, Emergency Department, SARS-CoV-2