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

NCT ID: NCT04303507

Last Updated: 2023-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 4652 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-29
• Study Completion Date: 2022-03-22

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Chloroquine or Hydroxychloroquine

Intervention Type: 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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

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

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Schilling, MD

Role: PRINCIPAL_INVESTIGATOR

Mahidol Oxford Tropical Medicine Research Unit

Locations

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

Bouaké, , 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, , 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

Countries

Benin; Côte d’Ivoire; Indonesia; Kenya; Mali; Nepal; Pakistan; Thailand; United Kingdom; Zambia

References

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.

Reference Type: DERIVED

PMID: 39264960 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37580026 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33570583 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.tropmedres.ac/covid-19/copcov

Related Info

Other Identifiers

VIR20001

Identifier Type: -

Identifier Source: org_study_id