Chloroquine Outpatient Treatment Evaluation for HIV-Covid-19

Study Overview
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Brief Summary
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Clinical manifestations of Covid-19 are poorly characterised in HIV co-infection, which may predispose to more severe disease. Reducing hospitalisation and severe illness in this population has important individual and public health benefits. The investigators propose a pragmatic multi-centre, randomized controlled trial in South Africa to evaluate the efficacy and safety of chloroquine or hydroxychloroquine to prevent progression of disease and hospitalisation amongst HIV-positive people with Covid-19 not requiring hospitalisation at initial assessment.

Detailed Description
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The trial objective is to compare chloroquine (or hydroxychloroquine) versus standard of care for the primary endpoint of hospitalisation or death at 28 days. Consenting adults who meet criteria for a Covid-19 person under investigation and who are ≥18 years, known to be HIV-positive, not requiring immediate hospitalisation and are not at risk of cardiac toxicities related to the study drug will be enrolled. The total sample size will be 560 participants (280 in each arm).

Official Title
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Multi-centre Randomised Controlled Trial of Chloroquine/Hydroxychloroquine Versus Standard of Care for Treatment of Mild Covid-19 in HIV-positive Outpatients in South Africa

Conditions
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Covid-19, HIV

Intervention / Treatment
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* Drug: Chloroquine or hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Tested for Covid-19 at a trial recruitment site as an outpatient; Age 18 years or older; Not requiring immediate hospitalisation; Mild disease, defined as respiratory rate <25/min, pulse rate <120/min, SpO2 >94%; HIV-positive by rapid test or documented history; Suspected or confirmed Covid-19; Signed informed consent. Exclusion Criteria: Covid-19 diagnosed > 5 days prior to randomization; Active tuberculosis; Need for concomitant drugs that are contraindicated with the use of Chloroquine/hydroxychloroquine; QTcF interval > 480 ms; Known glomerular filtration rate < 10 ml/min; Known with glucose-6-phosphate dehydrogenase deficiency (G6PD); Previous adverse drug reaction to investigational product; Concurrent involvement in other research or use of chloroquine, hydroxychloroquine or any other 4-aminoquinolone or another experimental investigational medicinal product that is likely to interfere with the study medication. Note: Pregnancy and breastfeeding are not exclusions for entry

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
Interventional Model Description: Pragmatic, multi-centre, open label, randomised controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Chloroquine or hydroxychloroquine<br>Loading dose of 4 tablets (150 mg chloroquine base per chloroquine salt tablet; 155 mg chloroquine base per hydroxychloroquine tablet) at time 0 and 6 hours, followed by a maintenance dose of 2 tablets at time 12 hours, and then twice daily for a total of 7 days. | Drug: Chloroquine or hydroxychloroquine<br>* Chloroquine has in vitro antiviral activity against many viruses, including SARS-CoV-1 and SARS-CoV-2. Chloroquine inhibits coronavirus replication at in vitro concentrations that are not cytotoxic and within a range of blood concentrations achievable during standard antimalarial treatment. Chloroquine inhibits viral replication through interference with glycosylation of coronavirus ACE2 receptors, required for viral entry, and downstream phagolysosome alkalisation, interfering with the low-pH-dependent steps of viral fusion and uncoating. Chloroquine also has anti-inflammatory properties and could provide benefit through this mechanism in Covid-19, where a cytokine storm has been described in critically ill patients. Hydroxychloroquine is a less toxic metabolite of chloroquine, has similar anti-inflammatory properties, and is more potent against SARS-CoV-2 in vitro.<br>|
| No Intervention: Arm 2: Standard of care<br>This does not include specific therapy under current guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival at 28 days post-randomization between experimental group and standard of care group | Events defined as Hospitalisation or Death | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious adverse events |  | Day 28 | 
| Incidence of adverse events of special interest related to investigational product at time of hospitalisation |  | Day 28 | 
| Premature discontinuation of treatment |  | Day 28 | 
| Time from treatment initiation to death, ARDS (PF/SF ratio < 300), or mechanical ventilation |  | Day 28 | 
| Proportion with moderate and severe ARDS |  | Day 28 | 
| Duration of hospitalisation and ICU stay in survivors |  | Day 28 | 
| Incidence of Covid-19 in household contacts |  | Day 28 |