Study of chloroquine/hydroxychloroquine and coronavirus disease (COVID-19) in the healthcare setting
| ISRCTN | ISRCTN10207947 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10207947 |
| EudraCT/CTIS number | 2020-001441-39 |
| IRAS number | 282109 |
| ClinicalTrials.gov number | NCT04303507 |
| Secondary identifying numbers | CPMS 45731, IRAS 282109 |
- Submission date
- 20/07/2020
- Registration date
- 21/07/2020
- Last edited
- 16/09/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Current plain English summary as of 03/06/2021:
Background and study aims
COVID-19 is a condition caused by the novel coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
The study team are working to find effective treatments and preventive measures as the pandemic grows. The risks to the healthcare system, as seen with SARS-CoV (SARS) previously, and then in Wuhan with COVID-19, could be a major threat to healthcare operations overall.
Chloroquine has significant antiviral activity against SARS-CoV-2 in laboratory cell culture, as it does for the related SARS-CoV. Several other laboratory studies confirm antiviral activities for chloroquine and hydroxychloroquine. This effect occurred when the drug was given either before or after the virus was added to the cells. This occurs at relatively high concentrations of these drugs when compared to the concentrations needed in the treatment of malaria. However, this concentration of the drugs needed for this effect could be achieved in humans with daily oral (via the mouth) treatment.
Chloroquine has complex properties, and so it is not known what amount of the drug would pass from the bloodstream to the lungs in order to have the necessary concentration to have the intended effect on the virus, although estimates can be made from studies in rats.
Hydroxychloroquine was synthesised first in 1946 and has largely replaced chloroquine for the management of autoimmune diseases as it has slightly reduced adverse effects (as toxicity and damage to the retina of the eyes only occurs at a higher concentration of the drug, and less abdominal discomfort is associated with the drug). It also has approximately twice the activity of chloroquine against the SARS-CoV-2 virus when inside the human body. Hydroxychloroquine may also cause less itching than chloroquine in dark skinned patients.
The study team think that chloroquine and hydroxychloroquine might both slow viral replication in SARS-CoV-2 exposed patients, therefore reducing or preventing the infection in these patients. even if they are shown not to work in treatment or in post exposure prophylaxis or in treatment. It is a basic principle of infectious diseases that preventing an infection developing requires lower doses or a less active drug than treatment.
In COVID-19 illness the total amount of the virus in the body is far greater than at the time of initial infection. Therefore the window of opportunity for antiviral medicines is at the earliest stages of infection. In addition laboratory studies show that this is when chloroquine and hydroxychloroquine have the greatest anti-viral activity in cells.
The study team believe these drugs may have the greatest use in preventing COVID-19 when given before infection as a preventative measure. These drugs are already in use in the prevention of other diseases, they are low-cost, and have been seen to be safe and well tolerated. If proven to be effective for this purpose, then it would be a readily deployable and affordable preventive measure for healthcare workers.
This study aims to determine if chloroquine or hydroxychloroquine given prior to infection can prevent symptomatic COVID-19 illness. The study will also investigate if there is an effect on the severity of COVID-19 infections, the prevention of asymptomatic COVID-19, and the prevention of acute respiratory infections (ARI) of all causes.
Who can participate?
The population to be studied comprises adult healthcare workers and other persons at risk of contracting COVID-19. These could include nurses, healthcare assistants (HCAs), doctors, pharmacists, physiotherapists, porters and anyone who is at risk of exposure to COVID-19. The study is planning to recruit globally including many countries in UK, Europe, Asia and Africa.
What does the study involve?
The participant will be randomised to receive either a dummy pill or treatment with chloroquine or hydroxychloroquine (the active drug used will vary by study site). Participants will receive a slightly larger amount of the study medication for the first dose and then will take a set amount of either the drug or the dummy pill for 3 months. Participants are followed up for a maximum for 5 months.
What are the possible benefits and risk of participating?
Risks related to chloroquine phosphate/ sulphate/ hydrochloride and hydroxychloroquine sulphate are very low, unless the drug is taken in overdose. These are very safe and generally well-tolerated medications but adverse reactions relating to the cardiovascular system, the central nervous system, the skin, the gastrointestinal (digestive) system, and low blood sugar, hypersensitivity, and retinal (part of the eye) toxicity have all been described. These adverse reactions usually occur after high doses or long-term exposures. Headache and gastrointestinal side-effects (e.g. nausea, diarrhea) are the most common adverse effects. Another adverse effect is itching, in particular with chloroquine, in dark-skinned individuals; Africans are much more commonly affected compared to Asians. These risks will be reduced by excluding participation if people have had a previous serious adverse reaction to chloroquine, or hydroxychloroquine, 4-aminoquinoline compounds, any components of the tablet or retinal or visual field changes of any kind.
Benefits of the study include access to a drug which may potentially prevent or reduce COVID-19 infection. No other proven preventive medication or vaccine exists currently exists or widely-available vaccine around the globe currently exists.
The main potential benefit is to the participant in the chloroquine or hydroxychloroquine arm (direct protection) but individuals in the placebo arm may benefit from indirect protection through the decreased ability of the infection to spread.
Participants should also be aware that their participation may lead to an intervention which may save many lives around the world or, alternatively, may show chloroquine or hydroxychloroquine prevention is ineffective so trials can move on to evaluate other possible drugs with a minimum of delay, and the use of these drugs around the world for this purpose can stop.
Where is the study run from?
Mahidol Oxford Tropical Medicine Research Unit (Thailand)
When is the study starting and how long is it expected to run for?
From April 2020 to March 2022
Who is funding the study?
Wellcome Trust (UK) ACT-Accelerator Therapeutics Partnership
Who is the main contact?
Dr William Schilling
William@tropmedres.ac
Previous plain English summary:
Background and study aims
COVID-19 is a condition caused by the novel coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
As of writing, SARS-CoV-2 has infected more than 7,000,000 individuals, killed more than 400,000 people and has spread to more than 200 countries and territories.
The study team are working to find effective treatments and preventive measures as the pandemic grows. The risks to the healthcare system, as seen with SARS-CoV (SARS) previously, and then in Wuhan with COVID-19, could be a major threat to healthcare operations overall.
Chloroquine has significant antiviral activity against SARS-CoV-2 in laboratory cell culture, as it does for the related SARS-CoV. Several other laboratory studies confirm antiviral activities for chloroquine and hydroxychloroquine. This effect occurred when the drug was given either before or after the virus was added to the cells. This occurs at relatively high concentrations of these drugs when compared to the concentrations needed in the treatment of malaria. However, this concentration of the drugs needed for this effect could be achieved in humans with daily oral (via the mouth) treatment.
Chloroquine has complex properties, and so it is not known what amount of the drug would pass from the bloodstream to the lungs in order to have the necessary concentration to have the intended effect on the virus, although estimates can be made from studies in rats.
Hydroxychloroquine was synthesised first in 1946 and has largely replaced chloroquine for the management of autoimmune diseases as it has slightly reduced adverse effects (as toxicity and damage to the retina of the eyes only occurs at a higher concentration of the drug, and less abdominal discomfort is associated with the drug). It also has approximately twice the activity of chloroquine against the SARS-CoV-2 virus when inside the human body. Hydroxychloroquine may also cause less itching than chloroquine in dark-skinned patients.
The study team think that chloroquine and hydroxychloroquine might both slow viral replication in SARS-CoV-2 exposed participants, therefore reducing or preventing the infection in these patients. even if they are shown not to work in treatment or in post-exposure prophylaxis or in treatment. It is a basic principle of infectious diseases that preventing an infection developing requires lower doses or a less active drug than treatment.
In COVID-19 illness the total amount of the virus in the body is far greater than at the time of initial infection. Therefore the window of opportunity for antiviral medicines is at the earliest stages of infection. In addition laboratory studies show that this is when chloroquine and hydroxychloroquine have the greatest anti-viral activity in cells.
The study team believe these drugs may have the greatest use in preventing COVID-19 when given before infection as a preventative measure. These drugs are already in use in the prevention of other diseases, they are low-cost, and have been seen to be safe and well-tolerated. If proven to be effective for this purpose, then it would be a readily deployable and affordable preventive measure for healthcare workers.
This study aims to determine if chloroquine or hydroxychloroquine given prior to infection can prevent symptomatic COVID-19 illness. The study will also investigate
if there is an effect on the severity of COVID-19 infections, the prevention of asymptomatic COVID-19, and the prevention of acute respiratory infections (ARI) of all causes.
Who can participate?
Healthcare workers and other staff working in a facility where there are cases of either proven or suspected COVID-19 can participate into the study. Adults from both genders aged less than 65 years will be enrolled in the study. Pregnant women and children are excluded from the study. The study is planning to recruit globally including many countries in UK, Europe, Asia and Africa.
What does the study involve?
The participant will be randomised to receive either a dummy pill or treatment with chloroquine or hydroxychloroquine (the active drug used will vary by study site). Participants will receive a slightly larger amount of the study medication for the first dose and then will take a set amount of either the drug or the dummy pill for 3 months. Participants are followed up for a maximum for 5 months.
What are the possible benefits and risk of participating?
Risks related to chloroquine phosphate/ sulphate/ hydrochloride and hydroxychloroquine sulphate are very low, unless the drug is taken in overdose. These are very safe and generally well-tolerated medications but adverse reactions relating to the cardiovascular system, the central nervous system, the skin, the gastrointestinal (digestive) system, and low blood sugar, hypersensitivity, and retinal (part of the eye) toxicity have all been described. THese adverse reactions usually occur after high doses or long-term exposures. The main adverse effect is itching, in particular with chloroquine, in dark-skinned individuals; Africans are much more commonly affected compared to Asians.
These risks will be reduced by excluding participation if people have had a previous serious adverse reaction to chloroquine, or hydroxychloroquine, 4-aminoquinoline compounds, any components of the tablet or retinal or visual field changes of any kind.
Benefits of the study include access to a drug which may potentially prevent or reduce COVID-19 infection. No other proven preventive medication or vaccine exists currently exists.
The main potential benefit is to the participant in the chloroquine or hydroxychloroquine arm (direct protection) but individuals in the placebo arm may benefit from indirect protection through the decreased ability of the infection to spread.
Participants should also be aware that their participation may lead to an intervention which may save many lives around the world or, alternatively, may show chloroquine or hydroxychloroquine prevention is ineffective so trials can move on to evaluate other possible drugs with a minimum of delay, and the use of these drugs around the world for this purpose can stop.
Where is the study run from?
Mahidol Oxford Tropical Medicine Research Unit (Thailand)
When is the study starting and how long is it expected to run for?
From April 2020 to April 2021
Who is funding the study?
Wellcome Trust (UK)
Who is the main contact?
Dr William Schilling
William@tropmedres.ac
Contact information
Scientific
Mahidol Oxford Tropical Medicine Research Unit
Bangkok
10400
Thailand
 ORCID ID |
0000-0002-6328-8748 |
|---|---|
| Phone | +66 2 203-6333 |
| William@tropmedres.ac |
Study information
| Study design | Multi-centre double-blind randomized placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Chloroquine/ hydroxychloroquine prevention of coronavirus disease (COVID-19) in the healthcare setting; a randomised, placebo-controlled prophylaxis study |
| Study acronym | COPCOV |
| Study hypothesis | It is hypothesised that chloroquine and hydroxychloroquine might both slow viral replication in exposed participants, attenuating or preventing the infection even if they are shown not to work in treatment or in post-exposure prophylaxis. |
| Ethics approval(s) | Approved 18/03/2020, Oxford Tropical Research Ethics Committee (OxTREC) (Research Services, University of Oxford, University Offices, Wellington Square, Oxford OX1 2JD; +44(0)1865 (2)82106; oxtrec@admin.ox.ac.uk), ref: 25-20 |
| Condition | COVID-19 (SARS-CoV-2 infection) |
| Intervention | Current interventions as of 03/06/2021: The study is a double-blind, randomised, placebo-controlled trial that will be conducted primarily in healthcare settings and other facilities directly involved in COVID-19 case management. We will recruit healthcare workers and other persons at risk of contracting COVID-19, who can be followed reliably for 5 months. The participant will be randomised to receive either chloroquine or placebo (1:1 randomisation), or to hydroxychloroquine or placebo (1:1 randomisation). A loading dose of 10mg base/kg (four 155 mg tablets for a 60 kg subject), followed by 155 mg daily (250 mg chloroquine phosphate salt/ 200 mg hydroxychloroquine sulphate) will be taken for 3 months. A randomisation list will be prepared by a statistician using block randomisation in a 1:1 ratio for the chloroquine/ hydroxychloroquine arm versus the placebo and stratified by site. The randomisation will be computer-generated and programmed in Stata 15. Previous interventions: The study will be conducted in healthcare settings and other facilities directly involved in COVID-19 case management. We will recruit healthcare workers and other staff working in a facility where there are cases of either proven, or suspected COVID-19, who can be followed reliably for 5 months. The participant will be randomised to receive either chloroquine or placebo (1:1 randomisation), or to hydroxychloroquine or placebo (1:1 randomisation). A loading dose of 10 mg base/kg (between three and five tablets e.g., four 155-mg tablets for a 60-kg subject), followed by 155 mg daily (250 mg chloroquine phosphate salt/200 mg hydroxychloroquine sulphate) will be taken for 3 months. A randomisation list will be prepared by a statistician using block randomisation in a 1:1 ratio for the chloroquine/ hydroxychloroquine arm versus the placebo and stratified by site. The randomisation will be computer-generated and programmed in Stata 15. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Current drug name(s) as of 03/06/2021: Chloroquine and hydroxychloroquine will be in the dose of 155 mg chloroquine base (250 mg of chloroquine phosphate or 200 mg of hydroxychloroquine sulphate) It is expected that chloroquine will be used in Asian sites and hydroxychloroquine in Europe and Africa, specific drug allocation will be determined by each participating country. Hydroxychloroquine sulphate will be used in the UK. Previous drug name(s): Chloroquine and hydroxychloroquine will be in the dose of 155 mg chloroquine base (250 mg of chloroquine phosphate or 200 mg of hydroxychloroquine sulphate) It is expected that chloroquine will be used in Asian sites and hydroxychloroquine in Europe, specific drug allocation will be determined by each participating country. Hydroxychloroquine sulphate will be used in the UK. |
| Primary outcome measure | The number of symptomatic COVID-19 infections will be compared between participants randomised to chloroquine or hydroxychloroquine, and placebo groups between baseline and 90 days |
| Secondary outcome measures | Current secondary outcome measures as of 28/01/2022: Secondary outcome measures 1. The symptoms severity and duration of COVID-19 illness, in those who become infected during the study will be compared between the two groups using a respiratory severity score between baseline and 90 days. 2. The number of asymptomatic cases of COVID-19 will be determined by comparing serology in all participants at time of enrolment and at the end of follow up. 3. The number and severity of symptomatic acute respiratory illnesses will be compared in participants randomised to chloroquine or hydroxychloroquine, and placebo groups between baseline and 90 days. Tertiary outcome measures 1. Genetic loci and levels of biochemical components will be correlated with occurrence of and disease severity of COVID-19 or other Acute Respiratory Infections (ARIs) between baseline and 90 days. 2. The days lost to work, and the relationship between the subjective assessment of wellbeing and the decision to self-isolate when unwell (i.e. not go to work) will be examined in relation to infection and treatment arm between baseline and 90 days. 3. The trial will collect data on use of health care resources and health related quality of life (EQ-5D-3L) to determine the effects between treatment groups between baseline and 90 days. Previous secondary outcome measures as of 03/06/2021: Secondary outcome measures 1. The symptoms severity and duration of COVID-19 illness, in those who become infected during the study will be compared between the two groups using a respiratory severity score between baseline and 90 days. 2. The number of asymptomatic cases of COVID-19 will be determined by comparing serology in all participants at time of enrolment and at the end of 5 months. 3. The number and severity of symptomatic acute respiratory illnesses will be compared in participants randomised to chloroquine or hydroxychloroquine, and placebo groups between baseline and 90 days. Tertiary outcome measures 1. Genetic loci and levels of biochemical components will be correlated with occurrence of and disease severity of COVID-19 or other Acute Respiratory Infections (ARIs) between baseline and 90 days. 2. The days lost to work, and the relationship between the subjective assessment of wellbeing and the decision to self-isolate when unwell (i.e. not go to work) will be examined in relation to infection and treatment arm between baseline and 90 days. 3. The trial will collect data on use of health care resources and health related quality of life (EQ-5D-3L) to determine the effects between treatment groups between baseline and 90 days. Previous secondary outcome measures: 1. The symptoms severity and duration of COVID-19 illness, in those who become infected during the study will be compared between the two groups using a respiratory severity score between baseline and 90 days 2. The number of asymptomatic cases of COVID-19 will be determined by comparing serology in all participants at time of enrolment and at the end of 5 months 3. The number and severity of symptomatic acute respiratory illnesses will be compared in participants randomised to chloroquine or hydroxychloroquine, and placebo groups between baseline and 90 days Tertiary outcome measures 1. Genetic loci and levels of biochemical components will be correlated with occurrence of and disease severity of COVID-19 or other Acute Respiratory Infections (ARIs) between baseline and 90 days 2. The days lost to work, and the relationship between the subjective assessment of well-being and the decision to self-isolate when unwell (i.e. not go to work) will be examined in relation to the infection and treatment arm between baseline and 90 days 3. Monetary costs associated with the use of healthcare resources between baseline and 90 days 4. Health-related quality of life measured using the quality of life questionnaire (EQ-5D-3L) at baseline and 90 days |
| Overall study start date | 29/04/2020 |
| Overall study end date | 21/03/2022 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | The initial aim was to recruit 40,000 participants and we predict an average of 400-800 participants per site in 50-100 sites. |
| Total final enrolment | 4646 |
| Participant inclusion criteria | Current participant inclusion criteria as of 03/06/2021: 1. Participant is willing and able to give informed consent for participation in the study and agrees with the study and its conduct 2. Agrees not to self-medicate with chloroquine, hydroxychloroquine or other potential antivirals 3. Adults (exact age is dependent on countries) less than 70 years old at the time of consent 4. Not previously diagnosed with COVID-19 5. Not currently symptomatic with an ARI 6. Participant is a healthcare worker or is a person at risk of contracting COVID-19. 7. Possesses an internet-enabled smartphone (Android or iOS) Previous participant inclusion criteria: 1. Willing and able to give informed consent for participation in the study and agrees with the study and its conduct 2. Agrees not to self-medicate with chloroquine, hydroxychloroquine or other potential antivirals 3. Adults (exact age is dependent on countries) <70 years old at the time of consent 4. Not previously diagnosed with COVID-19 5. Not currently symptomatic with an ARI 6. Working in a facility where there are cases of either proven or suspected COVID-19 7. Possesses an internet-enabled smartphone (Android or iOS) |
| Participant exclusion criteria | Current participant exclusion criteria as of 03/06/2021: 1. Hypersensitivity reaction to chloroquine, hydroxychloroquine or 4-aminoquinolines 2. Contraindication to taking chloroquine as prophylaxis e.g. known epileptic, known creatinine clearance <10 ml/min 3. Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines, or history of these medications within the previous 7 days 4. Taking any of the following prohibited medications: 4.1. Antiarrhythmic medications: digoxin, amiodarone, sotalol, flecainide 4.2. Antiparasitic/malarial agents: mefloquine, halofantrine, praziquantel 4.3. Antibiotics: levofloxacin, moxifloxacin, ciprofloxacin, azithromycin, clarithromycin, erythromycin 4.4. Antifungal drugs: fluconazole, ketoconazole, itraconazole, terfenadine 4.5. Psychoactive drugs: lithium, quetiapine, chlorpromazine, thioridazine, ziprasidone, haloperidol, droperidol, methadone 4.6. Migraine treatment: sumatriptan 4.7. Antihistamines: astemizole 4.8. Antiemetics: prochlorperazine, metoclopramide 4.9. Cancer treatments: abiraterone, dabrafenib, dacomitinib, enzalutamide, idelalisib, mitotane 4.10. Other specific drugs: ciclosporin, conivaptan, agalsidase alfa or beta, mifepristone, stiripentol 5. Known retinal disease 6. Inability to be followed up for the trial period 7. Known prolonged QT syndrome (however ECG is not required at baseline) 8. Known pregnancy or women who are actively trying to become pregnant 9. Prior diagnosis of porphyria 10. Previously received any dose of COVID-19 vaccine 11. The investigator may consult the physician’s guidance documents for any further questions regarding the eligibility of potential participants. Previous participant exclusion criteria: 1. Hypersensitivity reaction to chloroquine, hydroxychloroquine or 4-aminoquinolines 2. Contraindication to taking chloroquine as prophylaxis e.g. known epileptic, known creatinine clearance <10 ml/min 3. Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines 4. Taking a concomitant medication 5. Known retinal disease 6. Inability to be followed up for the trial period 7. Known prolonged QT syndrome (however ECG is not required at baseline) 8. Known pregnancy or women who are actively trying to become pregnant 9. Prior diagnosis of porphyria |
| Recruitment start date | 29/04/2020 |
| Recruitment end date | 21/12/2021 |
Locations
Countries of recruitment
- Benin
- England
- Ethiopia
- Indonesia
- Kenya
- Lao People's Democratic Republic
- Mali
- Niger
- Pakistan
- Thailand
- United Kingdom
- Zambia
Study participating centres
BN2 5BE
United Kingdom
OX3 9DU
United Kingdom
W2 1NY
United Kingdom
74800
Pakistan
Bangkok
10400
Thailand
Coventry
CV2 2DX
United Kingdom
LA9 7RG
United Kingdom
DY1 2HQ
United Kingdom
B1 3RB
United Kingdom
DN4 8QN
United Kingdom
Lusaka
-
Zambia
20231
Indonesia
20112
Indonesia
60115
Indonesia
60131
Indonesia
55281
Indonesia
-
Benin
Nairobi
-
Kenya
Eldoret
-
Kenya
BP 13330
Niger
Dharan
56700
Nepal
Allada
BP 559
Benin
BP 54378
Côte d'Ivoire
BP 1174
Côte d'Ivoire
Avenue Mohamed VI
Bamako
BP 251
Mali
Bamako
BP 3333
Mali
Sponsor information
University/education
Research Services
University of Oxford University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom
| Phone | +44 (0)1865 (2)82585 |
|---|---|
| research.services@admin.ox.ac.uk | |
| Website | http://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Research organisation
Private sector organisation / International organizations
- Location
- United Kingdom
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Private sector organisation / Trusts, charities, foundations (both public and private)
- Location
- Canada
Results and Publications
| Intention to publish date | 01/05/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | All publications will abide by the International Committee of Medical Journal Editors (ICMJE) recommendations of the role of authors and contributors. The results of the study will be summarised in lay language, in both English and the language(s) commonly spoken at the study sites, and disseminated to key stakeholders, user communities and caretakers of study participants. |
| IPD sharing plan | With the participant’s consent, clinical data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with other researchers to use in the future. Data generated from this study will adhere to the 2016 Statement on data sharing in public health emergencies (https://wellcome.ac.uk/press-release/statement-data-sharing-public-health-emergencies). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 6.0 | 13/01/2021 | 19/10/2022 | No | No |
| Statistical Analysis Plan | version 1.0 | 10/12/2022 | 27/07/2023 | No | No |
| Results article | 12/09/2024 | 16/09/2024 | Yes | No |
Additional files
Editorial Notes
16/09/2024: Publication reference added.
04/03/2024: The intention to publish date was changed from 01/02/2024 to 01/05/2024.
23/10/2023: The intention to publish date was changed from 31/10/2023 to 01/02/2024.
27/07/2023: This study was prospectively registered at ClinicalTrials.gov on 11/03/2020. The following changes were made to the study record:
1. Statistical analysis plan uploaded.
2. The intention to publish date was changed from 01/09/2023 to 31/10/2023.
15/06/2023: The intention to publish date has been changed from 31/12/2022 to 01/09/2023.
19/10/2022: Protocol uploaded (not peer reviewed).
28/01/2022: The following changes have been made:
1. The recruitment end date has been changed from 30/12/2021 to 21/12/2021.
2. The overall trial end date has been changed from 30/12/2021 to 21/03/2022.
3. The intention to publish date has been changed from 31/12/2021 to 31/12/2022.
4. The total final enrolment number has been added.
5. The phase has been changed from Phase III to Not Applicable.
6. The secondary outcome measures has been updated.
7. The trial participating centres "Mahosot hospital", "Metropolitan Medical Care Hospital", "Adam Malik Hospital", "Wahidin Hospital", "Hasanuddin University Hospital (UNHAS)", "Dadi Hospital", "Niamey (Epicentre France)", "Coast General Teaching and Referral Hospital", "The St. Paul's Hospital Millennium Medical College", "Alert Hospital", and "Zewditu Memorial Hospital" have been removed.
8. The trial participating centres "Niamey (Epicentre France)", "B.P. Koirala Institute of Health Sciences", "Hospital De Zone Allada", "University Hospital Center of Angre", "University Hospital Center of Bouake", "The Bamako Hospital of Dermatology", and "Hospital Of Mali" have been added.
9. The plain English summary has been updated to reflect the changes above.
10. Internal review.
03/06/2021: The following changes have been made:
1. The recruitment end date has been changed from 30/04/2021 to 30/12/2021.
2. The overall trial start date has been changed from 13/02/2020 to 29/04/2020.
3. The overall trial end date has been changed from 30/08/2021 to 30/12/2021.
4. The intention to publish date has been changed from 31/05/2021 to 31/12/2021.
5. The interventions have been updated.
6. The drug name(s) have been updated.
7. The secondary outcome measures have been updated.
8. The target number of participants has been changed from "40,000 total participants. UK sample size will be expected to be 8,000 to 10,000 participants." to "The initial aim was to recruit 40,000 participants and we predict an average of 400-800 participants per site in 50-100 sites.".
9. The participant inclusion criteria have been updated.
10. The participant exclusion criteria have been updated.
11. The countries of recruitment "Benin", "Ethiopia", "Kenya", "Mali", "Niger", and "Zambia" have been added.
12. The trial participating centres "The Dudley Group NHS Foundation Trust", "Birmingham & Solihull Mental Health NHS Trust", "Rotherham, Doncaster And South Humber NHS Foundation Trust", "Zambart", "Metropolitan Medical Care Hospital", "Murni Teguh Memorial Hospital", "Adam Malik Hospital", "Bunda Thamrin Hospital", "Airlangga University Hospital (UNAIR)", "Husada Utama Hospital", "Sardjito Hospital", "Wahidin Hospital", "Hasanuddin University Hospital (UNHAS)", "Dadi Hospital", "Centre Hospitalier et Universitaire de Zone Abomey-Calavi", "Coast General Teaching and Referral Hospital", "Mbagathi County Hospital", "Fountain Healthcare Hospital", "Centre for Vaccine Development-Mali", "Niamey (Epicentre France)", "The St. Paul's Hospital Millennium Medical College", Alert Hospital", and "Zewditu Memorial Hospital" have been added and the trial participating centre "RSUPN Cipto Mangunkusumo Hospital" has been removed.
13. The plain English summary has been updated.
09/10/2020: The following changes were made to the trial record:
1. The countries of recruitment Indonesia, Laos, Pakistan, Thailand were added.
2. The trial participating centres RSUPN Cipto Mangunkusumo Hospital, The Aga Khan University Hospital, Mahosot hospital, Faculty of Tropical Medicine, Mahidol University, University Hospitals Coventry and Warwickshire NHS Trust, University Hospitals of Morecambe Bay NHS Trust" were added.
20/07/2020: Trial’s existence confirmed by the National Institute of Health Research (NIHR).
