Acute Respiratory Distress Syndrome, ARDS, Corona Virus Infection, COVID-19
Conditions
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.
Interventions
DRUGHydroxychloroquine
Hydroxychloroquine; 200mg tablet; oral
OTHERPlacebo
Placebo; tablet; oral
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 494 |
| 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
Hydroxychloroquine: Hydroxychloroquine; 200mg tablet; oral | 495 |
| 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
Placebo: Placebo; tablet; oral | 494 |
| Total | 1,483 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not meet inclusion criteria after randomization | 4 | 2 | 1 |
Baseline characteristics
| Characteristic | Intervention Twice Weekly | Total | Intervention Once Weekly | Control Group |
|---|---|---|---|---|
| Age, Continuous | 41 years | 41 years | 42 years | 40 years |
| Race/Ethnicity, Customized Asian | 23 Participants | 75 Participants | 23 Participants | 29 Participants |
| Race/Ethnicity, Customized Black of African | 5 Participants | 20 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 22 Participants | 58 Participants | 18 Participants | 18 Participants |
| Race/Ethnicity, Customized Middle Eastern | 5 Participants | 15 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized Native American or Alaska Native | 7 Participants | 19 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 8 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized South Asian | 18 Participants | 47 Participants | 17 Participants | 12 Participants |
| Race/Ethnicity, Customized White or Caucasian | 421 Participants | 1271 Participants | 431 Participants | 419 Participants |
| Region of Enrollment Canada | 1 participants | 3 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 494 participants | 1480 participants | 493 participants | 493 participants |
| Sex: Female, Male Female | 258 Participants | 760 Participants | 261 Participants | 241 Participants |
| Sex: Female, Male Male | 237 Participants | 723 Participants | 233 Participants | 253 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 494 | 0 / 495 | 0 / 494 |
| other Total, other adverse events | 0 / 494 | 0 / 495 | 0 / 494 |
| serious Total, serious adverse events | 3 / 494 | 6 / 495 | 8 / 494 |
Outcome results
Primary
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.
Time frame: up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Once Weekly | COVID-19-free Survival | 464 Participants |
| Intervention Twice Weekly | COVID-19-free Survival | 468 Participants |
| Control Group | COVID-19-free Survival | 454 Participants |
Secondary
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.
Time frame: up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Once Weekly | Incidence of All-cause Study Medicine Discontinuation | 119 Participants |
| Intervention Twice Weekly | Incidence of All-cause Study Medicine Discontinuation | 158 Participants |
| Control Group | Incidence of All-cause Study Medicine Discontinuation | 133 Participants |
Secondary
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.
Time frame: up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Once Weekly | Incidence of Hospitalization for COVID-19 or Death | 3 Participants |
| Intervention Twice Weekly | Incidence of Hospitalization for COVID-19 or Death | 8 Participants |
| Control Group | Incidence of Hospitalization for COVID-19 or Death | 9 Participants |
Secondary
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.
Time frame: up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Once Weekly | Incidence of Possible COVID-19 Symptoms | 29 Participants |
| Intervention Twice Weekly | Incidence of Possible COVID-19 Symptoms | 28 Participants |
| Control Group | Incidence of Possible COVID-19 Symptoms | 38 Participants |
Secondary
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.
Time frame: up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Once Weekly | Incidence of Possible Study Medication-related Side Effects | 148 Participants |
| Intervention Twice Weekly | Incidence of Possible Study Medication-related Side Effects | 168 Participants |
| Control Group | Incidence of Possible Study Medication-related Side Effects | 100 Participants |
Secondary
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.
Time frame: up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Once Weekly | Number of Confirmed SARS-CoV-2 Detection | 29 Participants |
| Intervention Twice Weekly | Number of Confirmed SARS-CoV-2 Detection | 29 Participants |
| Control Group | Number of Confirmed SARS-CoV-2 Detection | 39 Participants |
Secondary
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.
Time frame: up to 12 weeks
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Intervention Twice Weekly | Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End | 1 score on a scale |
| Control Group | Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End | 1 score on a scale |