COVID-19Phase 3NCT04328467
Pre-exposure Prophylaxis for SARS-Coronavirus-2
A Phase 3 study testing Hydroxychloroquine in people with COVID-19 and Corona Virus Infection, run by University of Minnesota at 2 sites in United States.
Trial summary
Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Corona Virus Infection, ARDS
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,483 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Apr 2020to 13 Jul 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A healthcare worker at high risk for COVID-19 exposure (defined below):
- Persons primarily working in emergency departments (physicians, nurses, ancillary staff, triage personnel)
- Persons primarily working in intensive care units (physicians, nurses, ancillary staff, respiratory therapists)
- Persons performing aerosol generating procedures (i.e. anesthesiologists, nurse anesthetists (CRNAs)
- First responders (i.e. EMTs, paramedics)
Who cannot join
- Active COVID-19 disease
- Prior COVID-19 disease
- Current fever, cough, shortness of breath
- Allergy to chloroquine or hydroxychloroquine
- Prior retinal eye disease
- Known Chronic Kidney disease, Stage 4 or 5 or dialysis
Show all 11Show fewer
- Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency
- Weight <40 kg
- Prolonged QT syndrome
- Current use of hydroxychloroquine, chloroquine, or cardiac medicines of flecainide, amiodarone, digoxin, procainamide, or propafenone
- Current use of medications with known significant drug-drug interactions: artemether, lumefantrine, mefloquine, tamoxifen, or methotrexate.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Nationwide Enrollment via Internet, please email: covid19@umn.edu
Minneapolis, Minnesota, 55455
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.
Read the detailed description
The current standard of care is observation and quarantine after exposure to COVID-19. There is no approved treatment or prophylaxis for COVID-19.
As of March 6, 2020, the CDC estimates that the transmission of SARS-CoV2 after a U.S. household close contract is 10.5% (95%CI, 2.9 to 31.4%). Among all close contacts, the SARS-CoV2 transmission rate is estimated at 0.45% (95%CI, 0.12 to 1.6%) by the CDC. These estimates are based on monitoring of travel-associated COVID19 cases. Conversely, in a setting with community transmission, the secondary attack rate in China was 35% (95%CI, 27-44%) based on 48 transmissions among 137 persons in 9 index patients.
Chloroquine or Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or reduce disease severity. It is not known at what dosing hydroxychloroquine may be effective for pre-exposure prophylaxis.
- Being tested
- Hydroxychloroquine, Placebo
- Medical subject headings
- COVID-19, Coronavirus Infections, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Plaquenil
Hydroxychloroquine; 200mg tablet; oral
PlaceboOther
Placebo; tablet; oral
| Study group | Role | What they receive |
|---|---|---|
| Intervention Once Weekly | Experimental | 400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks Receives: Drug: Hydroxychloroquine |
| Intervention Twice Weekly | Experimental | 400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks Receives: Drug: Hydroxychloroquine |
| Control Group | Placebo comparator | Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
COVID-19-free Survival
Outcome reported as the number of participants in each arm who are COVID-19-free at the end of study treatment.
Measured: up to 12 weeks
Secondary outcomes (6)
Number of Confirmed SARS-CoV-2 Detection
Outcome reported as the number of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Measured: up to 12 weeks
Incidence of Possible COVID-19 Symptoms
Outcome reported as the count of participants in each arm who report COVID-19-related symptoms during study treatment.
Measured: up to 12 weeks
Incidence of All-cause Study Medicine Discontinuation
Outcome reported as the count of participants in each arm who discontinue study medication use for any reason during treatment.
Measured: up to 12 weeks
Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End
Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.
Measured: up to 12 weeks
Incidence of Hospitalization for COVID-19 or Death
Outcome reported as the number of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Measured: up to 12 weeks
Incidence of Possible Study Medication-related Side Effects
Outcome reported as the number of participants in each arm who experience possible medication-related side effects during study treatment.
Measured: up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2020
- Study start6 Apr 2020
- Primary completion13 Jul 2020
- Study completion13 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,483 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Radha Rajasingham, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04328467
- Sponsor's protocol ID
- MED-2020-28720
- Status last verified
- Jun 2021
- First submitted
- 27 Mar 2020
- Last updated
- 2 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Rajasingham R, Bangdiwala AS, Nicol MR, Skipper CP, Pastick KA, Axelrod ML, Pullen MF, Nascene AA, Williams DA, Engen NW, Okafor EC, Rini BI, Mayer IA, McDonald EG, Lee TC, Li P, MacKenzie LJ, Balko JM, Dunlop SJ, Hullsiek KH, Boulware DR, Lofgren SM; COVID PREP team. Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial. Clin Infect Dis. 2021 Jun 1;72(11):e835-e843. doi: 10.1093/cid/ciaa1571.
PubMed 33068425Lofgren SM, Nicol MR, Bangdiwala AS, Pastick KA, Okafor EC, Skipper CP, Pullen MF, Engen NW, Abassi M, Williams DA, Nascene AA, Axelrod ML, Lother SA, MacKenzie LJ, Drobot G, Marten N, Cheng MP, Zarychanski R, Schwartz IS, Silverman M, Chagla Z, Kelly LE, McDonald EG, Lee TC, Hullsiek KH, Boulware DR, Rajasingham R. Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19. Open Forum Infect Dis. 2020 Oct 19;7(11):ofaa500. doi: 10.1093/ofid/ofaa500. eCollection 2020 Nov.
PubMed 33204764
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04328467
- Acronym / sponsor ID
- MED-2020-28720
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,483 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 6 Apr 2020 (actual)
- Primary completion
- 13 Jul 2020 (actual)
- Study completion
- 13 Jul 2020 (actual)
- First posted
- 31 Mar 2020 (actual)
- Results
- Posted 30 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.
Detailed description
The current standard of care is observation and quarantine after exposure to COVID-19. There is no approved treatment or prophylaxis for COVID-19.
As of March 6, 2020, the CDC estimates that the transmission of SARS-CoV2 after a U.S. household close contract is 10.5% (95%CI, 2.9 to 31.4%). Among all close contacts, the SARS-CoV2 transmission rate is estimated at 0.45% (95%CI, 0.12 to 1.6%) by the CDC. These estimates are based on monitoring of travel-associated COVID19 cases. Conversely, in a setting with community transmission, the secondary attack rate in China was 35% (95%CI, 27-44%) based on 48 transmissions among 137 persons in 9 index patients.
Chloroquine or Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or reduce disease severity. It is not known at what dosing hydroxychloroquine may be effective for pre-exposure prophylaxis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Intervention Once Weekly | Experimental | Drug: Hydroxychloroquine400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks |
| Intervention Twice Weekly | Experimental | Drug: Hydroxychloroquine400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks |
| Control Group | Placebo comparator | Other: PlaceboPlacebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- A healthcare worker at high risk for COVID-19 exposure (defined below):
- Persons primarily working in emergency departments (physicians, nurses, ancillary staff, triage personnel)
- Persons primarily working in intensive care units (physicians, nurses, ancillary staff, respiratory therapists)
- Persons performing aerosol generating procedures (i.e. anesthesiologists, nurse anesthetists (CRNAs)
- First responders (i.e. EMTs, paramedics)
Key exclusion criteria (11 listed)
- Active COVID-19 disease
- Prior COVID-19 disease
- Current fever, cough, shortness of breath
- Allergy to chloroquine or hydroxychloroquine
- Prior retinal eye disease
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 |
|---|---|---|
| HydroxychloroquineAlso: PlaquenilHydroxychloroquine; 200mg tablet; oral | Drug | Intervention Once Weekly, Intervention Twice Weekly |
| PlaceboPlacebo; tablet; oral | Other | Control Group |
Primary outcome
COVID-19-free Survival
Time frame: up to 12 weeks
Outcome reported as the number of participants in each arm who are COVID-19-free at the end of study treatment.
6 secondary outcomes
Number of Confirmed SARS-CoV-2 Detection
Time frame: up to 12 weeks
Incidence of Possible COVID-19 Symptoms
Time frame: up to 12 weeks
Incidence of All-cause Study Medicine Discontinuation
Time frame: up to 12 weeks
Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End
Time frame: up to 12 weeks
Incidence of Hospitalization for COVID-19 or Death
Time frame: up to 12 weeks
Incidence of Possible Study Medication-related Side Effects
Time frame: up to 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33068425Rajasingham R, Bangdiwala AS, Nicol MR, Skipper CP, Pastick KA, Axelrod ML, Pullen MF, Nascene AA, Williams DA, Engen NW, Okafor EC, Rini BI, Mayer IA, McDonald EG, Lee TC, Li P, MacKenzie LJ, Balko JM, Dunlop SJ, Hullsiek KH, Boulware DR, Lofgren SM; COVID PREP team. Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial. Clin Infect Dis. 2021 Jun 1;72(11):e835-e843. doi: 10.1093/cid/ciaa1571.
- Derived from this study: PubMed 33204764Lofgren SM, Nicol MR, Bangdiwala AS, Pastick KA, Okafor EC, Skipper CP, Pullen MF, Engen NW, Abassi M, Williams DA, Nascene AA, Axelrod ML, Lother SA, MacKenzie LJ, Drobot G, Marten N, Cheng MP, Zarychanski R, Schwartz IS, Silverman M, Chagla Z, Kelly LE, McDonald EG, Lee TC, Hullsiek KH, Boulware DR, Rajasingham R. Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19. Open Forum Infect Dis. 2020 Oct 19;7(11):ofaa500. doi: 10.1093/ofid/ofaa500. eCollection 2020 Nov.
- Individual participant dataSharing planned: Undecided
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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.
Radha Rajasingham, MD principal investigator
University of Minnesota
2 sites 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 in people with COVID-19 and Corona Virus Infection, run by University of Minnesota at 2 sites in United States.
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 5 inclusion and 11 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: finished, as of the sponsor's last update on 2 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
Yes. Results are posted in the registry (first posted 30 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
COVID-19-free Survival (time frame: up to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04328467, which also lists 2 linked publications.
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 2 Jul 2021.