Hydroxychloroquine for Treatment of Non-Severe COVID-19

Study Overview
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Brief Summary
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Currently there are no proven treatments for COVID-19 and current standard therapy is supportive care with oxygen supplementation and treatment of symptoms. Several re-purposed and new drugs have been investigated but none is conclusive for efficacy against COVID-19 .Both Hydroxychloroquine(HCQ) and Chloroquine(CQ) have demonstrated activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have been investigated in small clinical trials with contradicting reports on their benefits or harm in treatment of COVID-19 .Several authors agree that the use of HCQ for treatment of COVID-19 needs to be assessed in large randomized controlled trials

Detailed Description
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Currently there are no proven treatments for COVID-19 and current standard therapy is supportive care with oxygen supplementation and treatment of symptoms. Several re-purposed and new drugs have been investigated but none is conclusive for efficacy against COVID-19.These include the antimalarial drugs- chloroquine(CQ) and hydroxychloroquine(HCQ), antivirals such as remdesivir and favipiravir and antiretroviral combination therapies such as lopinavir/ritonavir. Although hydroxychloroquine and chloroquine are readily accessible in Uganda and could be explore for treatment of COVID-19,current data regarding their efficacy and safety is scanty. It is necessary to determine whether HCQ can be useful for treatment of Ugandan patients with COVID-19 for the following reasons : Firstly, the Ugandan population expresses a high level of variability with a younger population with more than 50% under the age of 15 years. Secondly, the population with co-morbid conditions like diabetes mellitus ,hypertension and cardiovascular disease is significantly lower compared to higher income countries. Preliminary data from the first 52 COVID-19 patients in Uganda treated with HCQ demonstrated faster symptom resolution although this did not reach statistical significance. Lastly, HCQ has not been tested in mild-moderate disease where hospitalization is not necessary and we therefore do not know whether it can lead to faster viral clearance, slow disease progression and reduce time to symptom clearance. Our main aim will be to determine if hydroxychloroquine can lead to faster viral clearance.

Official Title
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The Efficacy and Safety of Hydroxychloroquine for the Treatment Of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial

Conditions
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Covid19

Intervention / Treatment
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* Drug: Hydroxychloroquine tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a confirmed positive Polymerase chain reaction(PCR) test for SARS COV-2 Adults of ≥ 18 years Evidence of a personally signed and dated informed consent document indicating that the participant(or their legal representative) has been informed of all pertinent aspects of the study Exclusion Criteria: Patients with contraindication to the use of hydroxychloroquine e.g. known allergy to hydroxychloroquine Patients enrolled in another interventional study which may interfere with study results Patients on medication that are known to have clinically significant interactions with the study drug e.g. digoxin, piperaquine, lumefantrine. Patients presenting with severe/critically ill COVID-19 (World Health Organization Ordinal scale for clinical improvement score of 5 or more) Patients with a fever( temperature ≥ 37.5 degrees centigrade) and a positive rapid diagnostic test (RDT) result for malaria Patients with corrected QT interval (QTc) prolongation of > 450ms for males and >470ms for females Pregnant or breastfeeding women Patients on chronic hydroxychloroquine use

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention arm<br>Participants will receive 400mg of hydroxychloroquine tablets 12-hourly on day 1 and 200mg 12-hourly on day 2 to day 5 in addition to standard of care treatment for COVID-19 | Drug: Hydroxychloroquine tablets<br>* Hydroxychloroquine tablets 400mg given orally 12 hourly on day 1 and 200mg 12 hourly on day 2 to 5<br>* Other names: HCQ;|
| No Intervention: Control arm<br>Participants will receive only standard of care treatment for COVID-19 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS COV-2 viral clearance | Attaining a negative PCR- test result i.e. 100% viral clearance | From randomization to day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical and laboratory adverse events | Grade 3 or 4 adverse events | From randomization to day 6 | 
| Time to symptom clearance | Time from randomization to symptom clearance | Randomization to day 10 | 
| Pharmacokinetic-pharmacodynamic model demonstrating drug concentration | Exposure-outcome relationship of hydroxychloroquine | Randomization to day 8 | 
| Sero-reversion to negative antibody test | Antibody sero-reversion | From randomization to day 90 |