COVID19, Coronavirus, Acute Respiratory Illnesses
Conditions
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.
Interventions
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
DRUGPlacebo
Placebo
Sponsors
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of symptomatic COVID-19 infections | Approximately 90 days | Number of symptomatic COVID-19 infections will be compared between the chloroquine or hydroxychloroquine and placebo groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptoms severity of COVID-19 | 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 | 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 | 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 | Approximately 90 days | Severity of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assess the impact of chloroquine or hydroxychloroquine prophylaxis on number of days lost to work during the pandemic. | 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 | 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) | 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. |
| Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity. | Approximately 90 days | Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, Acute Respiratory Infection and disease severity. |
Countries
Benin, Côte d’Ivoire, Indonesia, Kenya, Mali, Nepal, Pakistan, Thailand, United Kingdom, Zambia
Outcome results
None listed