PROLIFIC ChemoprophylaxisTrial (COVID-19)

Phase 3

• Conditions: COVID-19
• Interventions: Other: Matched Placebo Hydroxychloroquine; Drug: Hydroxychloroquine - Daily dosing; Drug: Hydroxychloroquine - Weekly Dosing

• Registration Number: NCT04352933
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust

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).

Study Timeline

• Study First Submitted: 2020-04-07
• Study First Submitted QC: 2020-04-15
• Study First Posted: 2020-04-20
• Status Verified: 2020-05
• Study Start: 2020-05-11
• Last Update Submitted: 2020-05-11
• Last Update Posted: 2020-05-13
• Primary Completion: 2020-10-31
• Study Completion: 2021-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1000

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Matched Placebo Hydroxychloroquine	Placebo arm - 2 tablets twice daily for first 2 days (loading phase), followed by 1 tablet every day for 90 days plus 2 tablets every 7th day, for approximately 90 days. Route: Oral. Pharmaceutical form: Tablet
Hydroxychloroquine - Daily dosing	Hydroxychloroquine - Daily dosing	Hydroxychloroquine Daily (loading phase: 800mg for first 2 days; maintenance phase: 1 x 200mg tablet every day) + weekly placebo, for approximately 90 days. Route: Oral. Pharmaceutical form: Tablet
Hydroxychloroquine - Weekly dosing	Hydroxychloroquine - Weekly Dosing	Hydroxychloroquine weekly (loading phase: 800mg for first 2 days; maintenance phase: 2 x 200mg tablets every 7th day/weekly) + daily placebo, for approximately 90 days. Route: Oral. Pharmaceutical form: Tablet

Primary Outcome Measures

Name	Time	Method
Time to positive COVID-19 disease	Assessed up to 90 days	Time taken for incidence of COVID-19 disease between Hydroxychloroquine and placebo arms

Secondary Outcome Measures

Name	Time	Method
Number of COVID-19 test positive cases	Assessed up to 90 days	Number of COVID-19 symptoms based on clinical guidelines and test positive infections per study arm
Number of COVID-19 serological test positive cases	Assessed up to 90 days	Number of test positive COVID-19 serological test positive cases per study arm
Severity of COVID-19 disease between each arm	Assessed up to 90 days	Severity based on hospitalisation
Number of common COVID-19 complications between each arm	Assessed up to 90 days	Number of common COVID-19 complications between arms

Trial Locations

Locations (1)

Cambridge University Hospitals NHS Foundation Trust; 🇬🇧 Cambridge, United Kingdom