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Pre-exposure Prophylaxis for SARS-Coronavirus-2

Primary Purpose

COVID-19, Corona Virus Infection, ARDS

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Hydroxychloroquine
Placebo
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- 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)

Exclusion Criteria:

  • 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
  • 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.

Sites / Locations

  • Nationwide Enrollment via Internet, please email: covid19@umn.edu
  • University of Minnesota

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Intervention Once Weekly

Intervention Twice Weekly

Control Group

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
March 27, 2020
Last Updated
June 30, 2021
Sponsor
University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT04328467
Brief Title
Pre-exposure Prophylaxis for SARS-Coronavirus-2
Official Title
Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
April 6, 2020 (Actual)
Primary Completion Date
July 13, 2020 (Actual)
Study Completion Date
July 13, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Corona Virus Infection, ARDS, Acute Respiratory Distress Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1483 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention Once Weekly
Arm Type
Experimental
Arm Description
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
Arm Title
Intervention Twice Weekly
Arm Type
Experimental
Arm Description
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
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
Plaquenil
Intervention Description
Hydroxychloroquine; 200mg tablet; oral
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo; tablet; oral
Primary Outcome Measure Information:
Title
COVID-19-free Survival
Description
Outcome reported as the number of participants in each arm who are COVID-19-free at the end of study treatment.
Time Frame
up to 12 weeks
Secondary Outcome Measure Information:
Title
Number of Confirmed SARS-CoV-2 Detection
Description
Outcome reported as the number of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Time Frame
up to 12 weeks
Title
Incidence of Possible COVID-19 Symptoms
Description
Outcome reported as the count of participants in each arm who report COVID-19-related symptoms during study treatment.
Time Frame
up to 12 weeks
Title
Incidence of All-cause Study Medicine Discontinuation
Description
Outcome reported as the count of participants in each arm who discontinue study medication use for any reason during treatment.
Time Frame
up to 12 weeks
Title
Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End
Description
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.
Time Frame
up to 12 weeks
Title
Incidence of Hospitalization for COVID-19 or Death
Description
Outcome reported as the number of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Time Frame
up to 12 weeks
Title
Incidence of Possible Study Medication-related Side Effects
Description
Outcome reported as the number of participants in each arm who experience possible medication-related side effects during study treatment.
Time Frame
up to 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - 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) Exclusion Criteria: 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Radha Rajasingham, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nationwide Enrollment via Internet, please email: covid19@umn.edu
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33068425
Citation
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.
Results Reference
result
PubMed Identifier
33204764
Citation
Lofgren 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.
Results Reference
derived

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Pre-exposure Prophylaxis for SARS-Coronavirus-2

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