Pre-exposure Prophylaxis for SARS-Coronavirus-2
Study Details
Study Description
Brief Summary
Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
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
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Intervention Once Weekly 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 |
Drug: Hydroxychloroquine
Hydroxychloroquine; 200mg tablet; oral
Other Names:
|
Experimental: Intervention Twice Weekly 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 |
Drug: Hydroxychloroquine
Hydroxychloroquine; 200mg tablet; oral
Other Names:
|
Placebo Comparator: Control Group 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 |
Other: Placebo
Placebo; tablet; oral
|
Outcome Measures
Primary Outcome Measures
- COVID-19-free Survival [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.
Secondary Outcome Measures
- Number of Confirmed SARS-CoV-2 Detection [up to 12 weeks]
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 [up to 12 weeks]
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 [up to 12 weeks]
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 [up to 12 weeks]
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 [up to 12 weeks]
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 [up to 12 weeks]
Outcome reported as the number of participants in each arm who experience possible medication-related side effects during study treatment.
Eligibility Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Nationwide Enrollment via Internet, please email: covid19@umn.edu | Minneapolis | Minnesota | United States | 55455 |
2 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
Sponsors and Collaborators
- University of Minnesota
Investigators
- Principal Investigator: Radha Rajasingham, MD, University of Minnesota
Study Documents (Full-Text)
More Information
Publications
None provided.- MED-2020-28720
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group |
---|---|---|---|
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral |
Period Title: Overall Study | |||
STARTED | 494 | 495 | 494 |
COMPLETED | 490 | 493 | 493 |
NOT COMPLETED | 4 | 2 | 1 |
Baseline Characteristics
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group | Total |
---|---|---|---|---|
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral | Total of all reporting groups |
Overall Participants | 494 | 495 | 494 | 1483 |
Age (years) [Mean (Inter-Quartile Range) ] | ||||
Mean (Inter-Quartile Range) [years] |
42
|
41
|
40
|
41
|
Sex: Female, Male (Count of Participants) | ||||
Female |
261
52.8%
|
258
52.1%
|
241
48.8%
|
760
51.2%
|
Male |
233
47.2%
|
237
47.9%
|
253
51.2%
|
723
48.8%
|
Race/Ethnicity, Customized (Count of Participants) | ||||
White or Caucasian |
431
87.2%
|
421
85.1%
|
419
84.8%
|
1271
85.7%
|
Black of African |
5
1%
|
5
1%
|
10
2%
|
20
1.3%
|
Asian |
23
4.7%
|
23
4.6%
|
29
5.9%
|
75
5.1%
|
Native Hawaiian or Pacific Islander |
0
0%
|
1
0.2%
|
1
0.2%
|
2
0.1%
|
Hispanic or Latino |
18
3.6%
|
22
4.4%
|
18
3.6%
|
58
3.9%
|
Native American or Alaska Native |
4
0.8%
|
7
1.4%
|
8
1.6%
|
19
1.3%
|
Middle Eastern |
6
1.2%
|
5
1%
|
4
0.8%
|
15
1%
|
South Asian |
17
3.4%
|
18
3.6%
|
12
2.4%
|
47
3.2%
|
Other |
3
0.6%
|
1
0.2%
|
4
0.8%
|
8
0.5%
|
Region of Enrollment (participants) [Number] | ||||
United States |
493
99.8%
|
494
99.8%
|
493
99.8%
|
1480
99.8%
|
Canada |
1
0.2%
|
1
0.2%
|
1
0.2%
|
3
0.2%
|
Outcome Measures
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group |
---|---|---|---|
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral |
Measure Participants | 494 | 495 | 494 |
Count of Participants [Participants] |
464
93.9%
|
468
94.5%
|
454
91.9%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group |
---|---|---|---|
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral |
Measure Participants | 494 | 495 | 494 |
Count of Participants [Participants] |
29
5.9%
|
29
5.9%
|
39
7.9%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group |
---|---|---|---|
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral |
Measure Participants | 494 | 495 | 494 |
Count of Participants [Participants] |
29
5.9%
|
28
5.7%
|
38
7.7%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group |
---|---|---|---|
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral |
Measure Participants | 494 | 495 | 494 |
Count of Participants [Participants] |
119
24.1%
|
158
31.9%
|
133
26.9%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Measure was only collected for one participant in the twice-weekly intervention group and one participant in the control group. No participants in the once-weekly intervention group were sampled for this measure. |
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group |
---|---|---|---|
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral |
Measure Participants | 0 | 1 | 1 |
Mean (Standard Deviation) [score on a scale] |
1
(NA)
|
1
(NA)
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group |
---|---|---|---|
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral |
Measure Participants | 494 | 495 | 494 |
Count of Participants [Participants] |
3
0.6%
|
8
1.6%
|
9
1.8%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group |
---|---|---|---|
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral |
Measure Participants | 494 | 495 | 494 |
Count of Participants [Participants] |
148
30%
|
168
33.9%
|
100
20.2%
|
Adverse Events
Time Frame | up to 12 weeks | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||
Arm/Group Title | Intervention Once Weekly | Intervention Twice Weekly | Control Group | |||
Arm/Group 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 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 Placebo: Placebo; tablet; oral | |||
All Cause Mortality |
||||||
Intervention Once Weekly | Intervention Twice Weekly | Control Group | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/494 (0%) | 0/495 (0%) | 0/494 (0%) | |||
Serious Adverse Events |
||||||
Intervention Once Weekly | Intervention Twice Weekly | Control Group | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/494 (0.6%) | 6/495 (1.2%) | 8/494 (1.6%) | |||
Cardiac disorders | ||||||
Chest Pain | 0/494 (0%) | 0 | 0/495 (0%) | 0 | 2/494 (0.4%) | 2 |
Heart Palpitations | 0/494 (0%) | 0 | 0/495 (0%) | 0 | 2/494 (0.4%) | 2 |
Tachycardia | 0/494 (0%) | 0 | 0/495 (0%) | 0 | 1/494 (0.2%) | 1 |
Atrial Fibrillation | 0/494 (0%) | 0 | 0/495 (0%) | 0 | 2/494 (0.4%) | 2 |
Endocrine disorders | ||||||
Hyperthyroid | 0/494 (0%) | 0 | 0/495 (0%) | 0 | 1/494 (0.2%) | 1 |
Gastrointestinal disorders | ||||||
Diverticulitis | 1/494 (0.2%) | 1 | 0/495 (0%) | 0 | 0/494 (0%) | 0 |
General disorders | ||||||
Other Not Specified | 0/494 (0%) | 0 | 2/495 (0.4%) | 2 | 0/494 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||
Motor Vehicle Accident | 0/494 (0%) | 0 | 1/495 (0.2%) | 1 | 0/494 (0%) | 0 |
Renal and urinary disorders | ||||||
Urinary Tract Infection | 0/494 (0%) | 0 | 1/495 (0.2%) | 1 | 1/494 (0.2%) | 1 |
Surgical and medical procedures | ||||||
Hysteroscopy | 1/494 (0.2%) | 1 | 0/495 (0%) | 0 | 0/494 (0%) | 0 |
Spinal Surgery | 1/494 (0.2%) | 1 | 0/495 (0%) | 0 | 0/494 (0%) | 0 |
Elective Coronary Angiogram | 0/494 (0%) | 0 | 1/495 (0.2%) | 1 | 0/494 (0%) | 0 |
Gall Bladder Surgery | 0/494 (0%) | 0 | 1/495 (0.2%) | 1 | 0/494 (0%) | 0 |
Sarcoidosis Biopsy | 0/494 (0%) | 0 | 0/495 (0%) | 0 | 1/494 (0.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
Intervention Once Weekly | Intervention Twice Weekly | Control Group | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/494 (0%) | 0/495 (0%) | 0/494 (0%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Radha Rajasingham, MD |
---|---|
Organization | University of Minnesota |
Phone | 612-626-8171 |
radha@umn.edu |
- MED-2020-28720