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

NCT04303507 | Completed DMC

• 1 other identifier: VIR20001
• Study Type: interventional
• Target: 4,652
• Locations: 10 countries
• Sites: 25

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.

Conditions

COVID19; Coronavirus; Acute Respiratory Illnesses

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Symptoms severity of COVID-19

  Approximately 90 days

• Number of asymptomatic cases of COVID-19

  Approximately 90 days

• Number of symptomatic acute respiratory illnesses

  Approximately 90 days

• Severity of symptomatic acute respiratory illnesses

  Approximately 90 days

Other Outcomes (4)

• Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity.

  Approximately 90 days

• Assess the impact of chloroquine or hydroxychloroquine prophylaxis on number of days lost to work during the pandemic.

  Approximately 90 days

• Assess the impact of chloroquine or hydroxychloroquine prophylaxis on healthcare costs

  Approximately 90 days

Study Arms (2)

Chloroquine or Hydroxychloroquine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Chloroquine or Hydroxychloroquine DRUG

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

Chloroquine or Hydroxychloroquine

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study and agrees with the study and its conduct
• Agrees not to self-medicate with chloroquine, hydroxychloroquine or other potential antivirals
• Adults (exact age is dependent on countries) less than 70 years old at the time of consent
• Not previously diagnosed with COVID-19
• Not currently symptomatic with an ARI
• Participant is a healthcare worker or is a person at risk of contracting COVID-19.
• Possesses an internet-enabled smartphone (Android or iOS)

You may not qualify if:

• Hypersensitivity reaction to chloroquine, hydroxychloroquine or 4-aminoquinolines
• Contraindication to taking chloroquine as prophylaxis e.g. known epileptic, known creatinine clearance \< 10 ml/min
• Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines, or history of these medications within the previous 7 days
• Taking prohibited medications
• Known retinal disease
• Inability to be followed up for the trial period
• Known prolonged QT syndrome (however ECG is not required at baseline)
• Known pregnancy or women who are actively trying to become pregnant
• Prior diagnosis of porphyria
• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (25)

Centre Hospitalier et Universitaire de Zone Abomey-Calavi

Abomey-Calavi, Benin

Location

Hospital De Zone Allada

Allada, Benin

Location

University Hospital Center of Angre

Abidjan, BP 54378, Côte d’Ivoire

Location

University Hospital Center of Bouake

Bouaké, BP 1174, Côte d’Ivoire

Location

Airlangga University Hospital (UNAIR)

Surabaya, East Java, 60115, Indonesia

Location

Husada Utama Hospital

Surabaya, East Java, 60131, Indonesia

Location

Bunda Thamrin Hospital

Medan, North Sumatra, 20112, Indonesia

Location

Murni Teguh Memorial Hospital

Medan, North Sumatra, 20231, Indonesia

Location

Sardjito Hospital

Yogyakarta, 55281, Indonesia

Location

Fountain Healthcare Hospital

Eldoret, Kenya

Location

Mbagathi County Hospital

Nairobi, Kenya

Location

The Bamako Hospital of Dermatology

Bamako, BP251, Mali

Location

Hospital Of Mali

Bamako, BP3333, Mali

Location

B.P. Koirala Institute of Health Sciences

Dharān, 56700, Nepal

Location

The Aga Khan University Hospital

Karachi, 74800, Pakistan

Location

Faculty of Tropical Medicine, Mahidol University

Bangkok, 10400, Thailand

Location

University Hospitals Of Morecambe Bay NHS Foundation Trust

Kendal, Cumbria, LA9 7RG, United Kingdom

Location

The Dudley Group NHS Foundation Trust

Dudley, West Midlands, DY1 2HQ, United Kingdom

Location

Birmingham & Solihull Mental Health NHS Trust

Birmingham, B1 3RB, United Kingdom

Location

Brighton and Sussex University Hospitals NHS Trust

Brighton, BN2 5BE, United Kingdom

Location

University Hospitals Coventry and Warwickshire NHS Trust

Coventry, CV2 2DX, United Kingdom

Location

Rotherham, Doncaster And South Humber NHS Foundation Trust

Doncaster, DN4 8QN, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Location

Oxford University Hospital NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

Location

Zambart

Lusaka, Zambia

Location

Related Publications (4)

• Winters J, Schilling WH. Approval delays in multi-country COVID-19 trials: the case of COPCOV and the risk of therapeutic inertia. Trials. 2025 Dec 16:10.1186/s13063-025-09300-z. doi: 10.1186/s13063-025-09300-z. Online ahead of print.

  PMID: 41402852 DERIVED

• Schilling WHK, Mukaka M, Callery JJ, Llewelyn MJ, Cruz CV, Dhorda M, Ngernseng T, Waithira N, Ekkapongpisit M, Watson JA, Chandna A, Nelwan EJ, Hamers RL, Etyang A, Beg MA, Sow S, Yavo W, Allabi AC, Basnyat B, Sharma SK, Amofa-Sekyi M, Yonga P, Adler A, Yuentrakul P, Cope T, Thaipadungpanit J, Rienpradub P, Imwong M, Abdad MY, Blacksell SD, Tarning J, Goudjo FF, Dossou AD, Konate-Toure A, Assi SB, Ouffoue K, Nasronudin N, Rachman BE, Romadhon PZ, Dewanto DD, Heryana MO, Novi T, Pasaribu AP, Mutiara M, Nasution MPR, Khairunnisa K, Dalimunthe FA, Airlangga E, Fahrezzy A, Subronto Y, Ananda NR, Rahardjani M, Rimainar A, Lucinde RK, Timbwa M, Onyango OE, Agutu C, Akech S, Hamaluba M, Kipyego J, Ngachi O, Haidara FC, Traore OY, Diarra F, Khanal B, Dahal P, Shrestha S, Rijal S, Kabore Y, Adehossi E, Guindo O, Qamar FN, Kazi AM, Woodrow CJ, Laird S, Cheeba M, Ayles H, Cheah PY, Taylor WRJ, Batty EM, Chotivanich K, Pukrittayakamee S, Phumratanaprapin W, von Seidlein L, Dondorp A, Day NPJ, White NJ; COPCOV Collaborative Group. Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial. PLoS Med. 2024 Sep 12;21(9):e1004428. doi: 10.1371/journal.pmed.1004428. eCollection 2024 Sep.

  PMID: 39264960 DERIVED

• Kabore Y, Vatrinet R, Guindo O, Moussa SH, Schilling WHK, Grais RF. Reflections on Participation in a Trial on Hydroxychloroquine as Prevention for COVID-19 among Health Workers in Niger. Am J Trop Med Hyg. 2023 Aug 14;109(3):511-514. doi: 10.4269/ajtmh.22-0606. Print 2023 Sep 6.

  PMID: 37580026 DERIVED

• 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.

  PMID: 33570583 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

Chloroquine; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• William Schilling, MD

  Mahidol Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 11, 2020
• Study Start: April 29, 2020
• Primary Completion: March 22, 2022
• Study Completion: March 22, 2022
• Last Updated: April 4, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

MA (2); ZA (1); KE (2); GB (8); BE (2); PA (1); TH (1); ID (5); NE (1); CÔ (2)