Chloroquine Outpatient Treatment Evaluation for HIV-Covid-19

NCT ID: NCT04360759

Last Updated: 2020-08-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-01
• Study Completion Date: 2021-06-30

Brief Summary

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

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).

Conditions

Covid-19; HIV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Chloroquine or hydroxychloroquine

Intervention Type: DRUG

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.

Arm 2: Standard of care

This does not include specific therapy under current guidelines.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cape Town

OTHER

Sponsor Role: lead

Responsible Party

Sean Wasserman

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sean Wasserman, MBChB

Role: PRINCIPAL_INVESTIGATOR

CIDRI-Africa, University of Cape Town

Graeme Meintjes, PhD

Role: PRINCIPAL_INVESTIGATOR

CIDRI-Africa, University of Cape Town

Locations

Khayelitsha Hospital

Cape Town, Western Cape, South Africa

Groote Schuur Hospital

Cape Town, Western Cape, South Africa

Countries

South Africa

Other Identifiers

HIV-COVID-19 CQOTE

Identifier Type: -

Identifier Source: org_study_id