Clinical trial NCT04352933: PROLIFIC ChemoprophylaxisTrial (COVID-19)
Official title: ChemoPROphyLaxIs For covId-19 Infectious Disease (the PROLIFIC Trial)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19
Keywords: SARS-CoV-2
Coronavirus
COVID-19
chemoprophylaxis
Hydroxychloroquine
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2020-04-20
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Time to positive COVID-19 disease
timeFrame: Assessed up to 90 days
Secondary outcomes:
measure: Number of COVID-19 test positive cases
timeFrame: Assessed up to 90 days
measure: Number of COVID-19 serological test positive cases
timeFrame: Assessed up to 90 days
measure: Severity of COVID-19 disease between each arm
timeFrame: Assessed up to 90 days
measure: Number of common COVID-19 complications between each arm
timeFrame: Assessed up to 90 days
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust
name: Joseph Cheriyan, MBCHB, FRCP
role: PRINCIPAL_INVESTIGATOR
References: