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

Primary Purpose

Covid-19, HIV

Status
Withdrawn
Phase
Phase 3
Locations
South Africa
Study Type
Interventional
Intervention
Chloroquine or hydroxychloroquine
Sponsored by
University of Cape Town
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid-19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Khayelitsha Hospital
  • Groote Schuur Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Arm 1: Chloroquine or hydroxychloroquine

Arm 2: Standard of care

Arm Description

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.

This does not include specific therapy under current guidelines.

Outcomes

Primary Outcome Measures

Event-free survival at 28 days post-randomization between experimental group and standard of care group
Events defined as Hospitalisation or Death

Secondary Outcome Measures

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

Full Information

First Posted
April 22, 2020
Last Updated
August 14, 2020
Sponsor
University of Cape Town
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1. Study Identification

Unique Protocol Identification Number
NCT04360759
Brief Title
Chloroquine Outpatient Treatment Evaluation for HIV-Covid-19
Acronym
CQOTE
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Equipoise for hydroxychloquine was lost
Study Start Date
May 1, 2020 (Anticipated)
Primary Completion Date
May 30, 2021 (Anticipated)
Study Completion Date
June 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cape Town

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid-19, HIV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Pragmatic, multi-centre, open label, randomised controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Chloroquine or hydroxychloroquine
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 2: Standard of care
Arm Type
No Intervention
Arm Description
This does not include specific therapy under current guidelines.
Intervention Type
Drug
Intervention Name(s)
Chloroquine or hydroxychloroquine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Event-free survival at 28 days post-randomization between experimental group and standard of care group
Description
Events defined as Hospitalisation or Death
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Incidence of serious adverse events
Time Frame
Day 28
Title
Incidence of adverse events of special interest related to investigational product at time of hospitalisation
Time Frame
Day 28
Title
Premature discontinuation of treatment
Time Frame
Day 28
Title
Time from treatment initiation to death, ARDS (PF/SF ratio < 300), or mechanical ventilation
Time Frame
Day 28
Title
Proportion with moderate and severe ARDS
Time Frame
Day 28
Title
Duration of hospitalisation and ICU stay in survivors
Time Frame
Day 28
Title
Incidence of Covid-19 in household contacts
Time Frame
Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sean Wasserman, MBChB
Organizational Affiliation
CIDRI-Africa, University of Cape Town
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Graeme Meintjes, PhD
Organizational Affiliation
CIDRI-Africa, University of Cape Town
Official's Role
Principal Investigator
Facility Information:
Facility Name
Khayelitsha Hospital
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7784
Country
South Africa
Facility Name
Groote Schuur Hospital
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7925
Country
South Africa

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

Chloroquine Outpatient Treatment Evaluation for HIV-Covid-19

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