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

Study Overview
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Brief Summary
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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.

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

Conditions
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COVID19, Coronavirus, Acute Respiratory Illnesses

Intervention / Treatment
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* Drug: Chloroquine or Hydroxychloroquine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 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) Exclusion Criteria: 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 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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroquine or Hydroxychloroquine<br>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<br>* 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<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 |