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

• ClinicalTrials.gov Identifier: NCT04303507
• Recruitment Status: Completed
• First Posted: March 11, 2020
• Last Update Posted: April 4, 2023
• Sponsor: University of Oxford
• Information provided by (Responsible Party): University of Oxford

Tracking Information

• First Submitted Date: March 6, 2020
• First Posted Date: March 11, 2020
• Last Update Posted Date: April 4, 2023
• Actual Study Start Date: April 29, 2020
• Actual Primary Completion Date: March 22, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2020)

Number of symptomatic COVID-19 infections [ Time Frame: Approximately 90 days ]

Number of symptomatic COVID-19 infections will be compared between the chloroquine or hydroxychloroquine and placebo groups

Original Primary Outcome Measures (submitted: March 10, 2020)

Number of symptomatic COVID-19 infections [ Time Frame: Approximately 100 days ]

Number of symptomatic COVID-19 infections will be compared in subjects randomised to chloroquine or placebo

Current Secondary Outcome Measures (submitted: April 24, 2020)

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

Original Secondary Outcome Measures (submitted: March 10, 2020)

• Symptoms severity of COVID-19 [ Time Frame: Approximately 100 days ]
  Symptoms severity of COVID-19 will be compared between the two groups using a respiratory severity score.
• Duration of COVID-19 [ Time Frame: Approximately 100 days ]
  Duration of COVID-19 will be compared between the two groups using a time to clinical improvement score.
• Number of asymptomatic cases of COVID-19 [ Time Frame: Approximately 100 days ]
  Number of asymptomatic cases of COVID-19 will be determined by comparing acute and convalescent serology in the two groups.
• Number of symptomatic acute respiratory illnesses [ Time Frame: Approximately 100 days ]
  The number of symptomatic acute respiratory illnesses will be compared in subjects randomised to chloroquine or placebo.
• Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity. [ Time Frame: Approximately 100 days ]
  Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity.

Current Other Pre-specified Outcome Measures (submitted: April 24, 2020)

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

Original Other Pre-specified Outcome Measures (submitted: March 10, 2020)

Drug exposure-protection relationship [ Time Frame: Approximately 100 days ]

Whole blood pre-dose chloroquine concentrations measured monthly will be correlated with disease protection (if any)

Descriptive Information

• Brief Title: 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)

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention

Condition

• COVID19
• Coronavirus
• Acute Respiratory Illnesses

Intervention

• 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 Arms

• 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

  Intervention: Drug: Chloroquine or Hydroxychloroquine
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 3, 2023): 4652
• Original Estimated Enrollment (submitted: March 10, 2020): 10000
• Actual Study Completion Date: March 22, 2022
• Actual Primary Completion Date: March 22, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Benin, Côte D'Ivoire, Indonesia, Kenya, Mali, Nepal, Pakistan, Thailand, United Kingdom, Zambia
• Removed Location Countries: Bangladesh, Ethiopia, Italy, Lao People's Democratic Republic, Niger

Administrative Information

• NCT Number: NCT04303507
• Other Study ID Numbers: VIR20001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• URL: https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing

• Current Responsible Party: University of Oxford
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Oxford
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: William Schilling, MD; Mahidol Oxford Tropical Medicine Research Unit

• PRS Account: University of Oxford
• Verification Date: May 2022