The number of confirmed cases of COVID-19 infectious disease arising from the SARS-CoV-2 coronavirus is rising substantially and rapidly, with the potential to overwhelm the ability of the entire National Health Service (NHS) to cope with the increased demand. The availability of personal protective equipment is limited and reports of high risk procedures such as aerosol generating procedures (e.g. intubation for the sickest patients) is a source of great concern for infection transmission. Frontline NHS staff with direct patient contact have the highest likelihood of exposure to SARS-CoV-2 and development of COVID-19 disease. Efforts to protect these workers from development of COVID-19, using drugs to prevent the disease, require urgent evaluation.
The number of confirmed cases of COVID-19 infectious disease arising from the SARS-CoV-2
coronavirus is rising substantially and rapidly, with the potential to overwhelm the ability
of the entire National Health Service (NHS) to cope with the increased demand. The
availability of personal protective equipment is limited and reports of high risk procedures
such as aerosol generating procedures (e.g. intubation for the sickest patients) is a source
of great concern for infection transmission. Frontline NHS staff with direct patient contact
have the highest likelihood of exposure to SARS-CoV-2 and development of COVID-19 disease.
Efforts to protect these workers from development of COVID-19, using drugs to prevent the
disease, require urgent evaluation.
This trial will be a double-blind, randomized, placebo-controlled trial in a cohort of
frontline healthcare workers, who will potentially be exposed to SARS-CoV-2. Eligible
participants will be frontline NHS workers aged 18 to 70 years who work in a healthcare
setting with direct patient care. Participants will be randomised to one of 3 arms and
receive either: (1) Hydroxychloroquine Daily (loading phase: 800mg for first 2 days;
maintenance phase: 1 x 200mg tablet every day) + weekly placebo; (2) Hydroxychloroquine
weekly (loading phase: 800mg for first 2 days; maintenance phase: 2 x 200mg tablets every 7th
day/weekly) + daily placebo, or (3) placebo (daily and weekly).
Participants will be reviewed at an interim visit 6 weeks after baseline and again and the
end of the study treatment in 90 days (approximately 3 months) after randomization.
Participants will also complete brief questions about their health weekly while on treatment
(remotely, via app/web/phone-based interface).
Drug: Hydroxychloroquine - Daily dosing
Active HCQ:
Days 1-2: Loading phase - 400mg (2 x 200mg capsules) taken TWICE A DAY for 2 days Days 3 onwards: Maintenance Phase - 200mg (1 x 200mg capsule) taken ONCE A DAY, every day for 90 days (~3 months),
Matched Placebo HCQ:
Days 3 onwards: Maintenance Phase - 2 capsules taken ONCE A WEEK on the same day each week (every 7th day) for 90 days (~3 months)
Drug: Hydroxychloroquine - Weekly Dosing
Active HCQ:
Days 1-2: Loading Phase - 400mg (2 x 200mg capsules) taken TWICE A DAY for 2 days Days 3 onwards: Maintenance Phase - 400mg (2 x 200mg capsules) taken ONCE A WEEK on the same day each week (every 7th day) for 90 days (~3 months)
Matched Placebo HCQ:
Days 3 onwards: Maintenance Phase - 1 capsule taken ONCE A DAY for 90 days (~3 months)
Other: Matched Placebo Hydroxychloroquine
Matched placebo HCQ - daily dosing:
Days 1-2: Loading Phase - 2 capsules taken TWICE A DAY for 2 days Days 3 onwards: Maintenance Phase - 1 capsule taken ONCE A DAY for 90 days (~3 months) Matched placebo HCQ - weekly dosing Days 3 onwards: Maintenance Phase - 2 capsules taken ONCE A WEEK on the same day each week (every 7th day) for 90 days (~3 months)
Inclusion Criteria:
To be included in the trial the participant MUST:
1. Have given written informed consent to participate
2. Be aged 18 years to 70 years
3. Not previously have been diagnosed with COVID-19
4. Work in a high-risk secondary or tertiary healthcare setting (hospitals accepting
COVID-19 patients) with direct patient-facing care
Exclusion Criteria:The presence of any of the following will mean participants are
ineligible:
1. Known COVID-19 positive test at baseline (if available)
2. Symptomatic for possible COVID-19 at baseline
3. Known hypersensitivity reaction to HCQ, chloroquine or 4-aminoquinolines
4. Known retinal disease
5. Known porphyria
6. Known chronic kidney disease (CKD; eGFR<30ml/min)
7. Known epilepsy
8. Known heart failure or conduction problems
9. Known significant liver disease (Gilbert's syndrome is permitted)
10. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
11. Currently taking any of the following contraindicated medications:
1. Digoxin
2. Chloroquine
3. Halofantrine
4. Amiodarone
5. Moxifloxacin
6. Cyclosporin
7. Mefloquine
8. Praziquantel
9. Ciprofloxacin
10. Clarithromycin
11. Prochlorperazine
12. Fluconazole
12. Currently taking hydroxychloroquine or having a clinical indication for taking
hydroxychloroquine
13. Currently breastfeeding
14. Unable to be followed-up during the trial
15. Current or future involvement in the active treatment phase of other interventional
research studies (excluding observational/non-interventional studies) before study
follow-up visit
16. Not able to use or have access to a modern phone device/web-based technology
17. Any other clinical reason which may preclude entry in the opinion of the investigator
Cambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom
Ella James, PhD
01223 349762
ella.james@addenbrookes.nhs.uk
Heike Templin
01223 250874
heike.templin@addenbrookes.nhs.uk
Joseph Cheriyan, MBCHB, FRCP, Principal Investigator
Cambridge University Hospitals NHS Foundation Trust