COVID-19
Conditions
Keywords
Hydroxychloroquine, Coronavirus Infections, Novel Coronavirus, Protective agents, Prophylaxis, Chemoprophylaxis, Severe Acute Respiratory Syndrome, Respiratory Distress Syndrome, Adult, Acute Lung Injury, Virus Diseases, Lung Diseases, Respiratory Tract Diseases, Respiration Disorders, Lung Injury, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Respiratory Tract Infections, Antimalarials, Antiprotozoal Agents, Antiparasitic Agents, Anti-Infective Agents, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antirheumatic Agents, Chloroquine, Chloroquine diphosphate
Brief summary
This is a double blind, placebo controlled study in approximately 2,000 health care workers at risk for being exposed to COVID-19. Eligible participants will be randomly assigned (1:1) to either treatment group (HCQ) or placebo in a double-blind fashion. Course of treatment is 30 days.
Detailed description
This is a double blind, placebo controlled study in approximately 2,000 health care workers at risk for being exposed to COVID-19. Eligible participants will be randomly assigned (1:1) to either treatment group (HCQ) or placebo in a double-blind fashion. After enrollment, baseline assessments will include nasopharyngeal swab for COVID-19 and a blood sample to detect seroconversion to COVID-19. For convenience, follow-up will be performed weekly through a direct to participant portal. A call center will provide support for any missed visits. Follow-up includes screening for any COVID-19 clinical infections, other respiratory infections, clinical events, adverse events, and Quality of Life (QoL) assessments. Course of treatment is 30 days. Participants are followed via survey weekly. At the end of treatment participants will return for repeat nasopharyngeal swab for COVID-19 and a blood sample to detect seroconversion to COVID-19. There will be one last contact at 8 weeks (2 months) from baseline.
Interventions
DRUGHydroxychloroquine
oral self administered tablet
DRUGPlacebo oral tablet
oral self administered tablet
Sponsors
Patient-Centered Outcomes Research Institute
Adrian Hernandez
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind
Intervention model description
Double blind, placebo-controlled, randomized clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusion: * Completed Informed Consent * Age ≥ 18 years old * Currently working in any environment in which there is a risk of exposure to patients with COVID-19 infections (healthcare worker)
Exclusion criteria
* Prior diagnosis of COVID-19 infection * Participation in another COVID-19 prophylaxis trial within 30 days of consent * Respiratory illness with new-onset fever (Temperature \> 100°F) or ongoing cough or dyspnea within 14 days * Known allergy to HCQ or chloroquine * Congenital prolonged QT syndrome * Current or planned use of QT prolonging drugs (e.g. procainamide, disopyramide, mexiletine, flecainide, propafenone, amiodarone, sotalol, cimetidine, dronedarone, dofetilide, levofloxacin, ciprofloxacin, moxifloxacin) and other contraindicated medications * End stage renal disease * Pre-existing retinopathy * Current or planned use of Hydroxychloroquine (study drug) for any indication Current or planned use of the following for treatment or prevention of COVID-19 infection: * Chloroquine * Azithromycin * Known cirrhosis or severe liver disease * History of severe skin reactions such as Steven-Johnson syndrome, toxic epidermal necrolysis * History of psoriasis or porphyria * Ventricular arrhythmias requiring medical treatment * Severe coronary artery disease or heart failure/cardiomyopathy with ongoing symptoms * Current or planned use of use of anti-seizure drugs * History of Glucose-6-phosphate dehydrogenase deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Infection With COVID-19 Infection | 30 days | This measure was a combination of confirmed infection and suspected infection. Confirmed clinical infection was defined as new-onset of fever or cough or dyspnea AND confirmed COVID-19 positive test result via local PCRI testing. Suspected infection was defined as new-onset fever or cough or dyspnea without local PCR testing due to local restrictions and/or testing policies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With COVID-19 Viral Shedding | 30 days | Number of participants with COVID-19 infection shedding via Covance swab PCR testing |
| Number of Participants With Serious Adverse Events (SAEs) or Hydroxychloroquine-Associated Events of Special Interest (EOSIs) | 30 days | Safety and Tolerability as determined by subject reported serious adverse events (SAEs) and hydroxychloroquine-associated events of special interest. EOSIs include: arrhythmias (ventricular), hepatic failure, bone marrow failure, aplastic anemia, prolonged QT interval, angioedema, dermatitis exfoliative, acute generalized exanthematous pustulosis, psychosis, suicidal ideation, seizure, methemoglobinemia. |
Countries
United States
Participant flow
Pre-assignment details
A participant was excluded from analysis population if they had a positive nasal swab test at baseline visit. This occurred to 1 participant assigned to the placebo group.
Participants by arm
| Arm | Count |
|---|---|
| Hydroxychloroquine Hydroxychloroquine tablet 600mg bid loading dose on day 1 followed by 400mg on days 2-30.
Hydroxychloroquine: oral self administered tablet | 683 |
| Placebo Matching placebo tablets
Placebo oral tablet: oral self administered tablet | 676 |
| Total | 1,359 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | positive nasal swab at baseline | 0 | 1 |
Baseline characteristics
| Characteristic | Hydroxychloroquine | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 11.9 | 43.6 years STANDARD_DEVIATION 11.6 | 43.1 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 39 Participants | 79 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 639 Participants | 1268 Participants | 629 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 12 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 55 Participants | 27 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 41 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 15 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 9 Participants | 3 Participants |
| Race (NIH/OMB) White | 624 Participants | 1234 Participants | 610 Participants |
| Region of Enrollment United States | 683 participants | 1359 participants | 676 participants |
| Sex: Female, Male Female | 442 Participants | 888 Participants | 446 Participants |
| Sex: Female, Male Male | 241 Participants | 471 Participants | 230 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 683 | 0 / 677 |
| other Total, other adverse events | 0 / 683 | 0 / 677 |
| serious Total, serious adverse events | 3 / 683 | 2 / 677 |
Outcome results
Primary
Number of Participants With Clinical Infection With COVID-19 Infection
This measure was a combination of confirmed infection and suspected infection. Confirmed clinical infection was defined as new-onset of fever or cough or dyspnea AND confirmed COVID-19 positive test result via local PCRI testing. Suspected infection was defined as new-onset fever or cough or dyspnea without local PCR testing due to local restrictions and/or testing policies.
Time frame: 30 days
Population: Participants who completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydroxychloroquine | Number of Participants With Clinical Infection With COVID-19 Infection | 41 Participants |
| Placebo | Number of Participants With Clinical Infection With COVID-19 Infection | 53 Participants |
p-value: 0.2Fisher Exact
Secondary
Number of Participants With COVID-19 Viral Shedding
Number of participants with COVID-19 infection shedding via Covance swab PCR testing
Time frame: 30 days
Population: Participants who completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydroxychloroquine | Number of Participants With COVID-19 Viral Shedding | 2 Participants |
| Placebo | Number of Participants With COVID-19 Viral Shedding | 2 Participants |
p-value: 1Regression, Linear
Secondary
Number of Participants With Serious Adverse Events (SAEs) or Hydroxychloroquine-Associated Events of Special Interest (EOSIs)
Safety and Tolerability as determined by subject reported serious adverse events (SAEs) and hydroxychloroquine-associated events of special interest. EOSIs include: arrhythmias (ventricular), hepatic failure, bone marrow failure, aplastic anemia, prolonged QT interval, angioedema, dermatitis exfoliative, acute generalized exanthematous pustulosis, psychosis, suicidal ideation, seizure, methemoglobinemia.
Time frame: 30 days
Population: Participants who completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydroxychloroquine | Number of Participants With Serious Adverse Events (SAEs) or Hydroxychloroquine-Associated Events of Special Interest (EOSIs) | 7 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) or Hydroxychloroquine-Associated Events of Special Interest (EOSIs) | 8 Participants |
p-value: 0.802Chi-squared