Clinical trial NCT04303507: Chloroquine/ Hydroxychloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting
Official title: Chloroquine/ Hydroxychloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting; a Randomised, Placebo-controlled Prophylaxis Study (COPCOV)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID19
Coronavirus
Acute Respiratory Illnesses
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2020-03-11
Enrollment: 4652
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of symptomatic COVID-19 infections
timeFrame: Approximately 90 days
Secondary outcomes:
measure: Symptoms severity of COVID-19
timeFrame: Approximately 90 days
measure: Number of asymptomatic cases of COVID-19
timeFrame: Approximately 90 days
measure: Number of symptomatic acute respiratory illnesses
timeFrame: Approximately 90 days
measure: Severity of symptomatic acute respiratory illnesses
timeFrame: Approximately 90 days
Other outcomes:
measure: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity.
timeFrame: Approximately 90 days
measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on number of days lost to work during the pandemic.
timeFrame: Approximately 90 days
measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on healthcare costs
timeFrame: Approximately 90 days
measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on quality of life measures using the quality of life questionnaire (EQ-5D-3L)
timeFrame: Approximately 90 days
Locations:
city: Abomey-Calavi
country: Benin
facility: Centre Hospitalier et Universitaire de Zone Abomey-Calavi
city: Allada
country: Benin
facility: Hospital De Zone Allada
city: Abidjan
country: Côte D'Ivoire
facility: University Hospital Center of Angre
city: Bouake
country: Côte D'Ivoire
facility: University Hospital Center of Bouake
city: Surabaya
country: Indonesia
facility: Airlangga University Hospital (UNAIR)
state: East Java
city: Surabaya
country: Indonesia
facility: Husada Utama Hospital
state: East Java
city: Medan
country: Indonesia
facility: Bunda Thamrin Hospital
state: North Sumatra
city: Medan
country: Indonesia
facility: Murni Teguh Memorial Hospital
state: North Sumatra
city: Yogyakarta
country: Indonesia
facility: Sardjito Hospital
city: Eldoret
country: Kenya
facility: Fountain Healthcare Hospital
city: Nairobi
country: Kenya
facility: Mbagathi County Hospital
city: Bamako
country: Mali
facility: The Bamako Hospital of Dermatology
city: Bamako
country: Mali
facility: Hospital Of Mali
city: Dharān Bāzār
country: Nepal
facility: B.P. Koirala Institute of Health Sciences
city: Karachi
country: Pakistan
facility: The Aga Khan University Hospital
city: Bangkok
country: Thailand
facility: Faculty of Tropical Medicine, Mahidol University
city: Kendal
country: United Kingdom
facility: University Hospitals Of Morecambe Bay NHS Foundation Trust
state: Cumbria
city: Dudley
country: United Kingdom
facility: The Dudley Group NHS Foundation Trust
state: West Midlands
city: Birmingham
country: United Kingdom
facility: Birmingham & Solihull Mental Health NHS Trust
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire NHS Trust
city: Doncaster
country: United Kingdom
facility: Rotherham, Doncaster And South Humber NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospital NHS Foundation Trust
city: Lusaka
country: Zambia
facility: Zambart
Study officials:
affiliation: Mahidol Oxford Tropical Medicine Research Unit
name: William Schilling, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Akhtar S, Das JK, Ismail T, Wahid M, Saeed W, Bhutta ZA. Nutritional perspectives for the prevention and mitigation of COVID-19. Nutr Rev. 2021 Feb 11;79(3):289-300. doi: 10.1093/nutrit/nuaa063.