Chloroquine Outpatient Treatment Evaluation for HIV-Covid-19 (CQOTE)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Covid-19; HIV
• Intervention / Treatment: Drug: Chloroquine or hydroxychloroquine

Detailed Description

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).

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Groote Schuur Hospital
    • Cape Town, Western Cape, South Africa, 7784
      • Khayelitsha Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Chloroquine or hydroxychloroquine; 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; 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.
No Intervention: Arm 2: Standard of care; This does not include specific therapy under current guidelines.

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: University of Cape Town
• Investigators: Principal Investigator: Sean Wasserman, MBChB, CIDRI-Africa, University of Cape Town; Principal Investigator: Graeme Meintjes, PhD, CIDRI-Africa, University of Cape Town

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): May 30, 2021
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 14, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Chloroquine; Hydroxychloroquine
• Other Study ID Numbers: HIV-COVID-19 CQOTE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data collected from this study may be made available to other international researchers and institutions who are working to control this Public Health Emergency, but in a fully anonymized way. No personal identifiers will be available anywhere in the data. Dates will either not be included or will be shifted by a random interval so as to not make it possible to trace any identity.
• IPD Sharing Time Frame: Recruitment period is planned for a maximum of 12 months, rate dependent on patient numbers. Additional sites will be opened after initial approvals.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No