Chloroquine Outpatient Treatment Evaluation for HIV-Covid-19

NCT04360759 | Withdrawn Phase 3 DMC

• 1 other identifier: HIV-COVID-19 CQOTE
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Covid-19; HIV

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (2)

Arm 1: Chloroquine or hydroxychloroquine

EXPERIMENTAL

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

Arm 2: Standard of care

NO INTERVENTION

This does not include specific therapy under current guidelines.

Interventions

Chloroquine or hydroxychloroquine 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 1: Chloroquine or hydroxychloroquine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Cape Town: lead

Study Sites (2)

Khayelitsha Hospital

Cape Town, Western Cape, 7784, South Africa

Location

Groote Schuur Hospital

Cape Town, Western Cape, 7925, South Africa

Location

MeSH Terms

Conditions

COVID-19

Interventions

Chloroquine; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sean Wasserman, MBChB

  CIDRI-Africa, University of Cape Town

  PRINCIPAL INVESTIGATOR

• Graeme Meintjes, PhD

  CIDRI-Africa, University of Cape Town

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Pragmatic, multi-centre, open label, randomised controlled trial

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: April 24, 2020
• Study Start: May 1, 2020
• Primary Completion: May 30, 2021
• Study Completion: June 30, 2021
• Last Updated: August 18, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• 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.

Locations

ZA (2)