PROLIFIC ChemoprophylaxisTrial (COVID-19)

NCT ID: NCT04352933

Last Updated: 2020-05-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-11
• Study Completion Date: 2021-04-30

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).

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine - Daily dosing

Intervention Type: DRUG

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)

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

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine - Weekly Dosing

Intervention Type: DRUG

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)

Placebo

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

Group Type: PLACEBO_COMPARATOR

Matched Placebo Hydroxychloroquine

Intervention Type: OTHER

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)

Interventions

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)

Intervention Type: 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)

Intervention Type: DRUG

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)

Intervention Type: OTHER

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Joseph Cheriyan, MD

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph Cheriyan, MBCHB, FRCP

Role: PRINCIPAL_INVESTIGATOR

Cambridge University Hospitals NHS Foundation Trust

Locations

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Ella James, PhD

Role: CONTACT

ella.james@addenbrookes.nhs.uk

01223 349762

Heike Templin

Role: CONTACT

heike.templin@addenbrookes.nhs.uk

01223 250874

Other Identifiers

PROLIFIC2020 (A095583)

Identifier Type: -

Identifier Source: org_study_id