Covid-19Phase 3CQOTENCT04360759
Chloroquine Outpatient Treatment Evaluation for HIV-Covid-19
A Phase 3 study testing Chloroquine or hydroxychloroquine in people with Covid-19 and HIV, run by University of Cape Town at 2 sites in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Chloroquine or hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesSouth Africa
- Study dates
- 1 May 2020to 30 Jun 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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
Trial locations and contacts
2 sites in 1 country.
South Africa2 sites
Khayelitsha Hospital
Cape Town, Western Cape, 7784
Groote Schuur Hospital
Cape Town, Western Cape, 7925
About this study
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
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.
Read the 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).
- Being tested
- Chloroquine or hydroxychloroquine
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chloroquine or hydroxychloroquineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Chloroquine or hydroxychloroquine |
| Arm 2: Standard of care | No intervention | This does not include specific therapy under current guidelines. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival at 28 days post-randomization between experimental group and standard of care group
Events defined as Hospitalisation or Death
Measured: Day 28
Secondary outcomes (7)
Incidence of serious adverse events
Measured: Day 28
Incidence of adverse events of special interest related to investigational product at time of hospitalisation
Measured: Day 28
Premature discontinuation of treatment
Measured: Day 28
Time from treatment initiation to death, ARDS (PF/SF ratio < 300), or mechanical ventilation
Measured: Day 28
Proportion with moderate and severe ARDS
Measured: Day 28
Duration of hospitalisation and ICU stay in survivors
Measured: Day 28
Incidence of Covid-19 in household contacts
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start1 May 2020 (estimated)
- Primary completion30 May 2021 (estimated)
- Study completion30 Jun 2021 (estimated)
Why it stopped: Equipoise for hydroxychloquine was lost
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pragmatic, multi-centre, open label, randomised controlled trial
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sean Wasserman, University of Cape Town
- Investigators
- Sean Wasserman, MBChB, Principal investigator, CIDRI-Africa, University of Cape TownGraeme Meintjes, PhD, Principal investigator, CIDRI-Africa, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04360759
- Sponsor's protocol ID
- HIV-COVID-19 CQOTE
- Acronym
- CQOTE
- Status last verified
- Aug 2020
- First submitted
- 22 Apr 2020
- Last updated
- 18 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04360759
- Acronym / sponsor ID
- CQOTE / HIV-COVID-19 CQOTE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Equipoise for hydroxychloquine was lost
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Study start
- 1 May 2020 (estimated)
- Primary completion
- 30 May 2021 (estimated)
- Study completion
- 30 Jun 2021 (estimated)
- First posted
- 24 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Pragmatic, multi-centre, open label, randomised controlled trial
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Chloroquine or hydroxychloroquine | Experimental | Drug: Chloroquine or hydroxychloroquineLoading 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 2: Standard of care | No intervention | –This does not include specific therapy under current guidelines. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chloroquine or hydroxychloroquineChloroquine 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. | Drug | Arm 1: Chloroquine or hydroxychloroquine |
Primary outcome
Event-free survival at 28 days post-randomization between experimental group and standard of care group
Time frame: Day 28
Events defined as Hospitalisation or Death
7 secondary outcomes
Incidence of serious adverse events
Time frame: Day 28
Incidence of adverse events of special interest related to investigational product at time of hospitalisation
Time frame: Day 28
Premature discontinuation of treatment
Time frame: Day 28
Time from treatment initiation to death, ARDS (PF/SF ratio < 300), or mechanical ventilation
Time frame: Day 28
Proportion with moderate and severe ARDS
Time frame: Day 28
Duration of hospitalisation and ICU stay in survivors
Time frame: Day 28
Incidence of Covid-19 in household contacts
Time frame: Day 28
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2020.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sean Wasserman, MBChB principal investigator
CIDRI-Africa, University of Cape Town
Graeme Meintjes, PhD principal investigator
CIDRI-Africa, University of Cape Town
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Chloroquine or hydroxychloroquine in people with Covid-19 and HIV, run by University of Cape Town at 2 sites in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival at 28 days post-randomization between experimental group and standard of care group (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2020.