COVID-19Phase 3NCT04352933
PROLIFIC ChemoprophylaxisTrial (COVID-19)
A Phase 3 study testing Hydroxychloroquine - Daily dosing and Hydroxychloroquine - Weekly Dosing in people with COVID-19, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- COVID-19
- What is being tested?
- Hydroxychloroquine - Daily dosing and Hydroxychloroquine - Weekly Dosing
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,000 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 May 2020to Apr 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- To be included in the trial the participant MUST:
- Have given written informed consent to participate
- Be aged 18 years to 70 years
- Not previously have been diagnosed with COVID-19
- 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:
Show all 35Show fewer
- Known COVID-19 positive test at baseline (if available)
- Symptomatic for possible COVID-19 at baseline
- Known hypersensitivity reaction to HCQ, chloroquine or 4-aminoquinolines
- Known retinal disease
- Known porphyria
- Known chronic kidney disease (CKD; eGFR<30ml/min)
- Known epilepsy
- Known heart failure or conduction problems
- Known significant liver disease (Gilbert's syndrome is permitted)
- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Currently taking any of the following contraindicated medications:
- Digoxin
- Chloroquine
- Halofantrine
- Amiodarone
- Moxifloxacin
- Cyclosporin
- Mefloquine
- Praziquantel
- Ciprofloxacin
- Clarithromycin
- Prochlorperazine
- Fluconazole
- Currently taking hydroxychloroquine or having a clinical indication for taking hydroxychloroquine
- Currently breastfeeding
- Unable to be followed-up during the trial
- Current or future involvement in the active treatment phase of other interventional research studies (excluding observational/non-interventional studies) before study follow-up visit
- Not able to use or have access to a modern phone device/web-based technology
- Any other clinical reason which may preclude entry in the opinion of the investigator
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
About this study
Official title: ChemoPROphyLaxIs For covId-19 Infectious Disease (the PROLIFIC Trial)
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.
Read the 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
- Being tested
- Hydroxychloroquine - Daily dosing, Hydroxychloroquine - Weekly Dosing, Matched Placebo Hydroxychloroquine
- Keywords
- SARS-CoV-2, Coronavirus, COVID-19, chemoprophylaxis, Hydroxychloroquine
- Medical subject headings
- COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine - Daily dosingDrug
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 DosingDrug
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)
Matched Placebo HydroxychloroquineOther
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)
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine - Daily dosing | Active comparator | 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 Receives: Drug: Hydroxychloroquine - Daily dosing |
| Hydroxychloroquine - Weekly dosing | Active comparator | 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 Receives: Drug: Hydroxychloroquine - Weekly Dosing |
| Placebo | Placebo comparator | 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 Receives: Other: Matched Placebo Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to positive COVID-19 disease
Time taken for incidence of COVID-19 disease between Hydroxychloroquine and placebo arms
Measured: Assessed up to 90 days
Secondary outcomes (4)
Number of COVID-19 test positive cases
Number of COVID-19 symptoms based on clinical guidelines and test positive infections per study arm
Measured: Assessed up to 90 days
Number of COVID-19 serological test positive cases
Number of test positive COVID-19 serological test positive cases per study arm
Measured: Assessed up to 90 days
Severity of COVID-19 disease between each arm
Severity based on hospitalisation
Measured: Assessed up to 90 days
Number of common COVID-19 complications between each arm
Number of common COVID-19 complications between arms
Measured: Assessed up to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2020
- Study start11 May 2020
- Primary completion31 Oct 2020 (estimated)
- Study completionApr 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph Cheriyan, MD, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Joseph Cheriyan, MBCHB, FRCP, Principal investigator, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04352933
- Sponsor's protocol ID
- PROLIFIC2020 (A095583)
- Status last verified
- May 2020
- First submitted
- 7 Apr 2020
- Last updated
- 13 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ChemoPROphyLaxIs For covId-19 Infectious Disease (the PROLIFIC Trial)
- ClinicalTrials.gov ID
- NCT04352933
- Acronym / sponsor ID
- PROLIFIC2020 (A095583)
- Conditions
- COVID-19
- Keywords
- SARS-CoV-2, Coronavirus, COVID-19, chemoprophylaxis, Hydroxychloroquine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Study start
- 11 May 2020 (actual)
- Primary completion
- 31 Oct 2020 (estimated)
- Study completion
- Apr 2021 (estimated)
- First posted
- 20 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine - Daily dosing | Active comparator | Drug: Hydroxychloroquine - Daily dosingHydroxychloroquine 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 | Active comparator | Drug: Hydroxychloroquine - Weekly DosingHydroxychloroquine 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 |
| Placebo | Placebo comparator | Other: Matched Placebo HydroxychloroquinePlacebo 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Have given written informed consent to participate
- Be aged 18 years to 70 years
- Not previously have been diagnosed with COVID-19
- 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:
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxychloroquine - Daily dosingActive 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 - Daily dosing |
| Hydroxychloroquine - Weekly DosingActive 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) | Drug | Hydroxychloroquine - Weekly dosing |
| Matched Placebo HydroxychloroquineMatched 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) | Other | Placebo |
Primary outcome
Time to positive COVID-19 disease
Time frame: Assessed up to 90 days
Time taken for incidence of COVID-19 disease between Hydroxychloroquine and placebo arms
4 secondary outcomes
Number of COVID-19 test positive cases
Time frame: Assessed up to 90 days
Number of COVID-19 serological test positive cases
Time frame: Assessed up to 90 days
Severity of COVID-19 disease between each arm
Time frame: Assessed up to 90 days
Number of common COVID-19 complications between each arm
Time frame: Assessed up to 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Cheriyan, MBCHB, FRCP principal investigator
Cambridge University Hospitals NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxychloroquine - Daily dosing and Hydroxychloroquine - Weekly Dosing in people with COVID-19, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ella James, PhD (01223 349762, ella.james@addenbrookes.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to positive COVID-19 disease (time frame: Assessed up to 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2020.