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 initial aim was to recruit 40,000 participants and we predict an average of 400-800 participants per site in 50-100 sites. 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 155mg tablets for a 60kg subject), followed by 155 mg daily (250mg chloroquine phosphate salt/ 200mg hydroxychloroquine sulphate) will be taken for 3 months. If the participant is diagnosed with COVID-19, they will take continue to take the study medication until: - 90 days after enrolment (i.e., completion of kit) - hospitalised due to COVID-19 disease (i.e., not for quarantine purposes) in which case they will stop, or - advised to stop by their healthcare professional for other reasons Episodes of symptomatic respiratory illness, including symptomatic COVID-19, and clinical outcomes will be recorded in the Case Record Form during the follow-up period. This study is funded by Wellcome Trust Grant reference 221307/Z/20/Z.
Drug: Chloroquine or Hydroxychloroquine
A loading dose of 10 mg base/ kg followed by 155 mg daily (250mg chloroquine phosphate salt or 200mg of or hydroxychloroquine sulphate) will be taken for 3 months
Drug: Placebo
Placebo
Study Participants The study population is adult healthcare workers and other persons
defined by the site investigator at risk of contracting COVID-19.
Inclusion Criteria
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)
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, or history of
these medications within the previous 7 days
4. Taking prohibited medications
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
The investigator may consult the physician's guidance documents for any further questions
regarding eligibility of potential participants.
Prohibited medications for the purpose of study enrollment include:
- Antiarrhythmic medications: digoxin, amiodarone, sotalol, flecainide
- Antiparasitic/malarial agents: mefloquine, halofantrine, praziquantel
- Antibiotics: levofloxacin, moxifloxacin, ciprofloxacin, azithromycin, clarithromycin,
erythromycin
- Antifungal drugs: fluconazole, ketoconazole, itraconazole, terfenadine
- Psychoactive drugs: lithium, quetiapine, chlorpromazine, thioridazine, ziprasidone,
haloperidol, droperidol, methadone
- Migraine treatment: sumatriptan
- Antihistamines: astemizole
- Antiemetics: prochlorperazine, metoclopramide
- Cancer treatments: abiraterone, dabrafenib, dacomitinib, enzalutamide, idelalisib,
mitotane
- Other specific drugs: ciclosporin, conivaptan, agalsidase alfa or beta, mifepristone,
stiripentol
PrincipaI Investigators will also be directed to crediblemeds.org to check other agents
that may prolong QT interval
Centre Hospitalier et Universitaire de Zone Abomey-Calavi
Abomey-Calavi, Benin
Hospital De Zone Allada
Allada, Benin
University Hospital Center of Angre
Abidjan, Côte D'Ivoire
University Hospital Center of Bouake
Bouake, Côte D'Ivoire
Airlangga University Hospital (UNAIR)
Surabaya, East Java, Indonesia
Husada Utama Hospital
Surabaya, East Java, Indonesia
Bunda Thamrin Hospital
Medan, North Sumatra, Indonesia
Murni Teguh Memorial Hospital
Medan, North Sumatra, Indonesia
Sardjito Hospital
Yogyakarta, Indonesia
Fountain Healthcare Hospital
Eldoret, Kenya
Mbagathi County Hospital
Nairobi, Kenya
The Bamako Hospital of Dermatology
Bamako, Mali
Hospital Of Mali
Bamako, Mali
B.P. Koirala Institute of Health Sciences
Dharān Bāzār, Nepal
The Aga Khan University Hospital
Karachi, Pakistan
Faculty of Tropical Medicine, Mahidol University
Bangkok, Thailand
University Hospitals Of Morecambe Bay NHS Foundation Trust
Kendal, Cumbria, United Kingdom
The Dudley Group NHS Foundation Trust
Dudley, West Midlands, United Kingdom
Birmingham & Solihull Mental Health NHS Trust
Birmingham, United Kingdom
Brighton and Sussex University Hospitals NHS Trust
Brighton, United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust
Coventry, United Kingdom
Rotherham, Doncaster And South Humber NHS Foundation Trust
Doncaster, United Kingdom
Imperial College Healthcare NHS Trust
London, United Kingdom
Oxford University Hospital NHS Foundation Trust
Oxford, United Kingdom
Zambart
Lusaka, Zambia
William Schilling, MD, Principal Investigator
Mahidol Oxford Tropical Medicine Research Unit