Chloroquine/ Hydroxychloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting (COPCOV)

Chloroquine/ Hydroxychloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting; a Randomised, Placebo-controlled Prophylaxis Study (COPCOV)

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.

Study Overview

• Status: Completed
• Conditions: Coronavirus; COVID19; Acute Respiratory Illnesses
• Intervention / Treatment: Drug: Placebo; Drug: Chloroquine or Hydroxychloroquine

• Study Type: Interventional
• Enrollment (Actual): 4652
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Benin
  • Abomey-Calavi, Benin
    • Centre Hospitalier et Universitaire de Zone Abomey-Calavi
  • Allada, Benin
    • Hospital De Zone Allada
• Côte D'Ivoire
  • Abidjan, Côte D'Ivoire, BP 54378
    • University Hospital Center of Angre
  • Bouake, Côte D'Ivoire, BP 1174
    • University Hospital Center of Bouake
• Indonesia
  • Yogyakarta, Indonesia, 55281
    • Sardjito Hospital
  • East Java
    • Surabaya, East Java, Indonesia, 60115
      • Airlangga University Hospital (UNAIR)
    • Surabaya, East Java, Indonesia, 60131
      • Husada Utama Hospital
  • North Sumatra
    • Medan, North Sumatra, Indonesia, 20112
      • Bunda Thamrin Hospital
    • Medan, North Sumatra, Indonesia, 20231
      • Murni Teguh Memorial Hospital
• Kenya
  • Eldoret, Kenya
    • Fountain Healthcare Hospital
  • Nairobi, Kenya
    • Mbagathi County Hospital
• Mali
  • Bamako, Mali, BP251
    • The Bamako Hospital of Dermatology
  • Bamako, Mali, BP3333
    • Hospital Of Mali
• Nepal
  • Dharān Bāzār, Nepal, 56700
    • B.P. Koirala Institute of Health Sciences
• Pakistan
  • Karachi, Pakistan, 74800
    • The Aga Khan University Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Faculty of Tropical Medicine, Mahidol University
• United Kingdom
  • Birmingham, United Kingdom, B1 3RB
    • Birmingham & Solihull Mental Health NHS Trust
  • Brighton, United Kingdom, BN2 5BE
    • Brighton and Sussex University Hospitals NHS Trust
  • Coventry, United Kingdom, CV2 2DX
    • University Hospitals Coventry and Warwickshire NHS Trust
  • Doncaster, United Kingdom, DN4 8QN
    • Rotherham, Doncaster And South Humber NHS Foundation Trust
  • London, United Kingdom, W2 1NY
    • Imperial College Healthcare NHS Trust
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospital NHS Foundation Trust
  • Cumbria
    • Kendal, Cumbria, United Kingdom, LA9 7RG
      • University Hospitals of Morecambe Bay NHS Foundation Trust
  • West Midlands
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • The Dudley Group NHS Foundation Trust
• Zambia
  • Lusaka, Zambia
    • Zambart

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: Chloroquine or Hydroxychloroquine; In Asia, the participant will receive chloroquine. In Europe, the participant will receive hydroxychloroquine Specific drug allocation will be determined by country prior to activation based upon factors such as inventory availability and importation requirements	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of symptomatic COVID-19 infections	Number of symptomatic COVID-19 infections will be compared between the chloroquine or hydroxychloroquine and placebo groups	Approximately 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms severity of COVID-19	Symptoms severity of COVID-19 will be compared between the two groups using a respiratory severity score.	Approximately 90 days
Number of asymptomatic cases of COVID-19	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.	Approximately 90 days
Number of symptomatic acute respiratory illnesses	Number of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.	Approximately 90 days
Severity of symptomatic acute respiratory illnesses	Severity of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.	Approximately 90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity.	Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, Acute Respiratory Infection and disease severity.	Approximately 90 days
Assess the impact of chloroquine or hydroxychloroquine prophylaxis on number of days lost to work during the pandemic.	Number of days lost to work in relation to the treatment arm	Approximately 90 days
Assess the impact of chloroquine or hydroxychloroquine prophylaxis on healthcare costs	The trial will collect data on monetary costs associated with the use of healthcare resources and determine the effects between treatment groups.	Approximately 90 days
Assess the impact of chloroquine or hydroxychloroquine prophylaxis on quality of life measures using the quality of life questionnaire (EQ-5D-3L)	The trial will collect data on health-related quality of life using the quality of life questionnaire (EQ-5D-3L) to determine the effects between treatment groups.	Approximately 90 days

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: William Schilling, MD, Mahidol Oxford Tropical Medicine Research Unit

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2020
• Primary Completion (Actual): March 22, 2022
• Study Completion (Actual): March 22, 2022

Study Registration Dates

• First Submitted: March 6, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Chloroquine; Hydroxychloroquine
• Other Study ID Numbers: VIR20001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: With participant's consent, suitably anonymised 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No