PROLIFIC ChemoprophylaxisTrial (COVID-19)

COVID-19 Clinical Trial

Official title:

ChemoPROphyLaxIs For covId-19 Infectious Disease (the PROLIFIC Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04352933
• Other study ID #: PROLIFIC2020 (A095583)
• Status: Recruiting
• Phase: Phase 3
• Start date: May 11, 2020
• Est. completion date: April 2021

Study information

• Verified date: May 2020
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: Ella James, PhD
• Phone: 01223 349762
• Email: ella.james[@]addenbrookes.nhs.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: April 2021
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

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)
• 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)

Locations

Country	Name	City	State
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
Cambridge University Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to positive COVID-19 disease	Time taken for incidence of COVID-19 disease between Hydroxychloroquine and placebo arms	Assessed up to 90 days
Secondary	Number of COVID-19 test positive cases	Number of COVID-19 symptoms based on clinical guidelines and test positive infections per study arm	Assessed up to 90 days
Secondary	Number of COVID-19 serological test positive cases	Number of test positive COVID-19 serological test positive cases per study arm	Assessed up to 90 days
Secondary	Severity of COVID-19 disease between each arm	Severity based on hospitalisation	Assessed up to 90 days
Secondary	Number of common COVID-19 complications between each arm	Number of common COVID-19 complications between arms	Assessed up to 90 days