Acute Respiratory Distress Syndrome, Coronavirus, Corona Virus Infection, Coronavirus Infections, SARS-CoV Infection
Conditions
Keywords
COVID-19, Corona Virus, SARS-COV-2, Coronavirus
Brief summary
Study Objective: 1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
Detailed description
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing COVID19. The current strategy uses a public health model of identifying infected cases, isolation, and quarantine to stop transmission. Once exposed, observation is standard-of-care. Therapy is generally not given to persons who are not hospitalized. The doses of hydroxychloroquine being used are within the normal standard FDA-approved doses. Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or early preemptive therapy may decrease disease severity. This trial will use a modification of standard malaria dosing of hydroxychloroquine to provide post-exposure prophylaxis to prevent disease or preemptive therapy for those with early symptoms. People around the the United States and Canada can participate to help answer this critically important question. No in-person visits are needed. This trial is targeting 5 groups of people NATIONWIDE to participate: 1. If you are symptomatic with a positive COVID-19 test within the first 4 days of symptoms and are not hospitalized; OR 2. If you live with someone who has been diagnosed with COVID-19, with your last exposure within the last 4 days, and do not have any symptoms; OR 3. If you live with someone who has been diagnosed with COVID-19, and your symptoms started within the last 4 days; OR 4. If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 4 days and do not have symptoms; OR 5. If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 4 days AND have compatible symptoms starting within the last 4 days; You may participate if you live anywhere in the United States (including territories) or in the Canadian Provinces of Quebec, Manitoba, Alberta, or Ontario. For information on how to participate in the research trial, go to covidpep.umn.edu or email covid19@umn.edu for instructions. Please check your spam folder if you email. In Canada, for trial information, please go to: www.covid-19research.ca
Interventions
DRUGHydroxychloroquine
200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days
OTHERPlacebo
4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Sponsors
McGill University Health Centre/Research Institute of the McGill University Health Centre
University of Manitoba
University of Alberta
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Asymptomatic participants are randomized and analyzed separate from symptomatic participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent * Exposure to a COVID19 case within 4 days as either a household contact or occupational exposure, OR * Symptomatic COVID19 case with confirmed diagnosis within 4 days of symptom onset OR symptomatic high risk exposure with known COVID19 contact and within 4 days of symptom onset;
Exclusion criteria
* Current hospitalization * Allergy to hydroxychloroquine * Retinal eye disease * Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency * Known chronic kidney disease, stage 4 or 5 or receiving dialysis * Structural or ischemic heart disease * Personal or Family History of Prolonged QT syndrome * Weight \< 50 kg * Known Porphyria * Current use of: hydroxychloroquine or cardiac medicines of: flecainide, Tambocor; amiodarone, Cordarone, Pacerone; digoxin or Digox, Digitek, Lanoxin; procainamide or Procan, Procanbid, propafenone, Rythmal, sotalol; * Current use of medicines which prolong the QT interval including: * Antimicrobials: levofloxacin, ciprofloxacin, moxifloxacin, azithromycin, clarithromycin, erythromycin, ketoconazole, itraconazole, or mefloquine * Antidepressants: amitriptyline, citalopram, desipramine, escitalopram, imipramine, doxepin, fluoxetine, wellbutrin, or venlafaxine * Antipsychotic or mood stabilizers: haloperidol, droperidol, lithium, quetiapine, thioridazine, ziprasidone * Methadone * Sumatriptan, zolmitriptan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline | 14 days | Number of participants at 14 days post enrollment with active COVID19 disease among those who were asymptomatic at baseline. |
| Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline | baseline and 14 days | Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Confirmed SARS-CoV-2 Detection | 14 days | Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection. |
| Occurrence of Symptoms Compatible With COVID-19 (Possible Disease) | 14 days | Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID-19 infection. |
| Rate of Hospitalization | 14 days | Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease. |
| Overall Symptom Severity at 5 and 14 Days | 5 and 14 days | Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe) |
| Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry | 14 days | Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the number of participants who report a score of 3. |
| Rate of All-Cause Study Medicine Discontinuation or Withdrawal | 14 days | Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason. |
| Rate of Death | Approximately 30 days | Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease through study completion of 14 days. For those hospitalized within the 14-day study period, the protocol specified follow up would occur for up to 90 days to capture the final outcome of participants' hospitalization. Approximately 30-days was the maximal follow up for hospitalization outcome needed in the trial. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Participants in this arm will receive the study drug.
Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days | 658 |
| Placebo Participants in this arm will receive a placebo treatment.
Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days | 654 |
| Total | 1,312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 32 | 38 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo | Total | Treatment |
|---|---|---|---|
| Age, Continuous | 42 years STANDARD_DEVIATION 12 | 42 years STANDARD_DEVIATION 12 | 42 years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian/South Asian | 206 Participants | 410 Participants | 204 Participants |
| Race/Ethnicity, Customized Black or African American | 24 Participants | 52 Participants | 28 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 36 Participants | 73 Participants | 37 Participants |
| Race/Ethnicity, Customized Middle Eastern | 9 Participants | 23 Participants | 14 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 4 Participants | 9 Participants | 5 Participants |
| Race/Ethnicity, Customized Unknown/Not Reported | 10 Participants | 22 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 379 Participants | 742 Participants | 363 Participants |
| Region of Enrollment Canada | 29 Participants | 59 Participants | 30 Participants |
| Region of Enrollment United States | 625 Participants | 1253 Participants | 628 Participants |
| Sex: Female, Male Non-binary Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Non-binary Male | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Sex Female | 336 Participants | 690 Participants | 354 Participants |
| Sex: Female, Male Sex Male | 314 Participants | 614 Participants | 300 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 658 | 1 / 654 |
| other Total, other adverse events | 367 / 658 | 148 / 654 |
| serious Total, serious adverse events | 6 / 658 | 11 / 654 |
Outcome results
Primary
Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline
Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Time frame: baseline and 14 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline | -2.6 score on a scale | Standard Error 0.12 |
| Placebo | Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline | -2.33 score on a scale | Standard Error 0.12 |
p-value: 0.11795% CI: [-0.61, 0.27]Mixed Models Analysis
Primary
Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline
Number of participants at 14 days post enrollment with active COVID19 disease among those who were asymptomatic at baseline.
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline | 49 Participants |
| Placebo | Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline | 58 Participants |
p-value: 0.3595% CI: [-7, 2.2]Fisher Exact
Secondary
Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry
Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the number of participants who report a score of 3.
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry | 5 Participants |
| Placebo | Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry | 8 Participants |
Secondary
Occurrence of Symptoms Compatible With COVID-19 (Possible Disease)
Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID-19 infection.
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Occurrence of Symptoms Compatible With COVID-19 (Possible Disease) | 48 Participants |
| Placebo | Occurrence of Symptoms Compatible With COVID-19 (Possible Disease) | 55 Participants |
Secondary
Overall Symptom Severity at 5 and 14 Days
Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Time frame: 5 and 14 days
Population: Early preemptive treatment trial (n=423 symptomatic participants with data)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment | Overall Symptom Severity at 5 and 14 Days | Day 5 | -2.22 score on a scale |
| Treatment | Overall Symptom Severity at 5 and 14 Days | Day 14 | -3.36 score on a scale |
| Placebo | Overall Symptom Severity at 5 and 14 Days | Day 5 | -2.05 score on a scale |
| Placebo | Overall Symptom Severity at 5 and 14 Days | Day 14 | -3.08 score on a scale |
Secondary
Rate of All-Cause Study Medicine Discontinuation or Withdrawal
Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Rate of All-Cause Study Medicine Discontinuation or Withdrawal | 97 Participants |
| Placebo | Rate of All-Cause Study Medicine Discontinuation or Withdrawal | 63 Participants |
Secondary
Rate of Confirmed SARS-CoV-2 Detection
Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Rate of Confirmed SARS-CoV-2 Detection | 11 Participants |
| Placebo | Rate of Confirmed SARS-CoV-2 Detection | 9 Participants |
Secondary
Rate of Death
Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease through study completion of 14 days. For those hospitalized within the 14-day study period, the protocol specified follow up would occur for up to 90 days to capture the final outcome of participants' hospitalization. Approximately 30-days was the maximal follow up for hospitalization outcome needed in the trial.
Time frame: Approximately 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Rate of Death | 1 Participants |
| Placebo | Rate of Death | 1 Participants |
Secondary
Rate of Hospitalization
Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Rate of Hospitalization | 5 Participants |
| Placebo | Rate of Hospitalization | 9 Participants |