Coronavirus, Covid19
Conditions
Keywords
fluvoxamine
Brief summary
The purpose of this research study is to determine if a drug called fluvoxamine can be used early in the course of the COVID-19 infection to prevent more serious complications like shortness of breath. Fluvoxamine is an anti-depressant drug approved by the FDA for the treatment of obsessive-compulsive disorder. The use of fluvoxamine for the treatment of COVID-19 is considered investigational, which means the US Food and Drug Administration has not approved it for this use. This study is fully-remote, which means that there is no face-to-face contact; study materials including study drug will be shipped to participants' houses. People around the United States and Canada can participate.
Detailed description
The investigators will randomize approximately 880 participants, age 30 and older, who have tested tested positive for COVID-19 and are currently experiencing mild symptoms. People around the United States and Canada can participate. All interactions for this study will be conducted remotely by videoconferencing, email, or phone. Screening: All participants will first complete a pre-screen to see if they may be eligible for the study. Once a participant is confirmed eligible and consented, the study team will send the study materials. These materials will consist of study medication and self-monitoring equipment, including an oxygen saturation monitor, blood pressure monitor, and thermometer. RCT: Participants will be randomly assigned (1:1) to take either fluvoxamine or a placebo. This phase of the study will last approximately 15 days and is double-blinded. Participants will take up to 100mg of fluvoxamine or placebo by mouth twice a day for a daily total of 200mg. Participants will continue this dose for approximately 15 days. Depending on tolerability, the dose may be adjusted. Participants will also complete short 5 minute assessments daily to report the results of self-monitoring (including oxygen level, blood pressure, and temperature), a shortness of breath rating and any adverse events. Follow-up Phase: The study team will follow participants for approximately 90 days after the end of the randomized phase. If needed, the study team will review medical records to determine the clinical course of participants.
Interventions
DRUGFluvoxamine
Up to 200mg per day (2 capsules per day) as tolerated, for approximately 15 days
DRUGPlacebo
Will take 2 capsules per day as tolerated for approximately 15 days
Sponsors
Covid-19 Early Treatment Fund
McGill University
Cures Within Reach
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and woman age 30 and older; 2. Not currently hospitalized 3. Proven SARS-CoV-2 positive (per lab or physician report). 4. Currently symptomatic with one or more of the following symptoms: fever, cough, myalgia, mild dyspnea, chest pain, diarrhea, nausea, vomiting, anosmia (inability to smell), ageusia (inability to taste), sore throat, nasal congestion. 5. Able to provide informed consent. 6. Upon initial screening, participant reports one of the following risk factors for clinical deterioration: age≥40, racial/ethnic group African-American, Hispanic, or Native American (including more than one race), or 1+ of the following medical conditions which increase risk for developing moderate-severe COVID illness: obesity, hypertension, diabetes, heart disease (coronary artery disease, history of myocardial infarction, or heart failure), lung disease (eg asthma, COPD), immune disorder (eg rheumatoid arthritis, lupus).
Exclusion criteria
1. Illness severe enough to require hospitalization or already meeting study's primary endpoint for clinical worsening (eg current O2 saturation \<92% on room air, current use of supplemental oxygen to maintain O2 saturation ≥92%). 2. Unstable medical comorbidities (eg decompensated cirrhosis), per patient report and/or medical records. 3. Immunocompromised from the following: solid organ transplant, BMT, high dose steroids (\>20mg prednisone per day), or tocilizumab 4. Already enrolled in another COVID 19 medication trial (not including vaccination or prophylaxis trials) 5. Unable to provide informed consent 6. Unable to perform the study procedures 7. Taking donepezil (rationale: donepezil is a S1R agonist), or sertraline (rationale: sertraline is a strong sigma-1 antagonist). 8. Taking warfarin-also known as Coumadin (rationale: increased risk of bleeding), phenytoin (rationale: fluvoxamine inhibits its metabolism), clopidogrel (rationale: fluvoxamine inhibits its metabolism from pro-drug to active drug which raises risk of cardiovascular events), and St John's wort (rationale: fluvoxamine + St John's wort are considered contraindicated because of the risk of serotonin syndrome) 9. Taking SSRIs, SNRIs, or tricyclic antidepressants, unless these are at a low dose such that a study investigator concludes that a clinically significant interaction with fluvoxamine (ie either serotonin syndrome or TCA overdose) is unlikely (examples: participant takes escitalopram but only at 5-10mg daily; that dose plus 200mg fluvoxamine would be insufficient to cause serotonin syndrome; or, participant takes amitriptyline but only at 25mg nightly; even if fluvoxamine inhibits its metabolism, it would be an insufficient dose to cause QTc prolongation or problematic side effects). 10. Individuals who report they have bipolar disorder or are taking medication for bipolar disorder (lithium, valproate, high-dose antipsychotic), unless the investigator concludes that the risk for mania is unlikely (ie it is doubtful that the patient actually has bipolar disorder). 11. Individuals who take alprazolam or diazepam and are unwilling to cut the medication by 25% (rationale: fluvoxamine modestly inhibits the metabolism of these drugs). 12. Participants taking theophylline, tizanidine, clozapine, or olanzapine (drugs with a narrow therapeutic index that are primarily metabolized by CYP 1A2, which is inhibited by fluvoxamine) will be reviewed with a study investigator and excluded unless the investigator concludes that the risk to the participant is low (this would be unlikely; example: participant takes tizanidine only as needed and is willing to avoid it for the 15 days of the study). 13. Received vaccine for COVID-19.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Deterioration | RCT-approximately 15 days | Defined as the number of participants who experienced the following: both of the following: 1)Presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, 2)) decrease in O2 saturation (\<92% on room air) and/or supplemental oxygen requirement to keep O2 saturation ≥92%). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluvoxamine Start fluvoxamine 50mg capsule once, then 100mg twice daily. May reduce dose for tolerability reasons. Will be followed in the RCT for approximately 15 days.
Fluvoxamine: Up to 200mg per day (2 capsules per day) as tolerated, for approximately 15 days | 272 |
| Placebo Start placebo one capsule, twice daily. May reduce dose for tolerability reasons. Will be followed in RCT for approximately 15 days.
Placebo: Will take 2 capsules per day as tolerated for approximately 15 days | 275 |
| Total | 547 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Could not confirm baseline status | 6 | 2 |
| Overall Study | Could not confirm started study medication | 15 | 15 |
| Overall Study | Deteriorated at or before baseline assessment | 6 | 9 |
| Overall Study | Drop out and did not start medication | 15 | 17 |
| Overall Study | Other | 2 | 4 |
| Overall Study | Started medication more than 7 days after symptom onset | 18 | 14 |
Baseline characteristics
| Characteristic | Placebo | Fluvoxamine | Total |
|---|---|---|---|
| Age, Customized Age | 48 years STANDARD_DEVIATION 9.83 | 48 years STANDARD_DEVIATION 10.18 | 48 years STANDARD_DEVIATION 10 |
| Body Mass Index category (BMI) 25-29.9 | 90 Participants | 86 Participants | 176 Participants |
| Body Mass Index category (BMI) Greater than or equal to 30 | 123 Participants | 115 Participants | 238 Participants |
| Body Mass Index category (BMI) Less than 25 | 62 Participants | 71 Participants | 133 Participants |
| Coexisting conditions Active cancer | 1 Participants | 0 Participants | 1 Participants |
| Coexisting conditions Asthma | 33 Participants | 40 Participants | 73 Participants |
| Coexisting conditions Diabetes | 28 Participants | 23 Participants | 51 Participants |
| Coexisting conditions Heart disease | 4 Participants | 4 Participants | 8 Participants |
| Coexisting conditions Hepatitis B/C | 1 Participants | 1 Participants | 2 Participants |
| Coexisting conditions HIV | 4 Participants | 1 Participants | 5 Participants |
| Coexisting conditions Hypertension | 62 Participants | 55 Participants | 117 Participants |
| Coexisting conditions Immune disorder | 4 Participants | 14 Participants | 18 Participants |
| Coexisting conditions Kidney disease | 2 Participants | 1 Participants | 3 Participants |
| Coexisting conditions Liver disease | 1 Participants | 1 Participants | 2 Participants |
| Coexisting conditions Lung disease | 2 Participants | 2 Participants | 4 Participants |
| Coexisting conditions Other medical conditions | 54 Participants | 42 Participants | 96 Participants |
| Coexisting conditions Thyroid problem | 27 Participants | 20 Participants | 47 Participants |
| Duration of Covid-19 symptoms | 4.8 days STANDARD_DEVIATION 1.52 | 5 days STANDARD_DEVIATION 1.44 | 4.9 days STANDARD_DEVIATION 1.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 37 Participants | 35 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 236 Participants | 234 Participants | 470 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Most severe COVID-19 symptom at baseline Body aches | 30 Participants | 27 Participants | 57 Participants |
| Most severe COVID-19 symptom at baseline Chills | 10 Participants | 9 Participants | 19 Participants |
| Most severe COVID-19 symptom at baseline Cough | 37 Participants | 34 Participants | 71 Participants |
| Most severe COVID-19 symptom at baseline Diarrhea | 9 Participants | 8 Participants | 17 Participants |
| Most severe COVID-19 symptom at baseline Fatigue | 59 Participants | 70 Participants | 129 Participants |
| Most severe COVID-19 symptom at baseline Loss of appetite | 26 Participants | 21 Participants | 47 Participants |
| Most severe COVID-19 symptom at baseline Loss of smell | 91 Participants | 74 Participants | 165 Participants |
| Most severe COVID-19 symptom at baseline Loss of taste | 48 Participants | 47 Participants | 95 Participants |
| Most severe COVID-19 symptom at baseline Nasal congestion | 30 Participants | 45 Participants | 75 Participants |
| Most severe COVID-19 symptom at baseline Nausea | 4 Participants | 11 Participants | 15 Participants |
| Most severe COVID-19 symptom at baseline Shortness of breath | 7 Participants | 6 Participants | 13 Participants |
| Most severe COVID-19 symptom at baseline Sore throat | 7 Participants | 8 Participants | 15 Participants |
| Most severe COVID-19 symptom at baseline Subjective fever | 18 Participants | 12 Participants | 30 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 8 Participants | 6 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 8 Participants | 13 Participants |
| Race/Ethnicity, Customized Black/African American | 23 Participants | 22 Participants | 45 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Other (identified as other) | 21 Participants | 29 Participants | 50 Participants |
| Race/Ethnicity, Customized South Asian | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Unknown/Not reported | 22 Participants | 17 Participants | 39 Participants |
| Race/Ethnicity, Customized White/Caucasian | 201 Participants | 197 Participants | 398 Participants |
| Sex: Female, Male Female | 170 Participants | 169 Participants | 339 Participants |
| Sex: Female, Male Male | 105 Participants | 103 Participants | 208 Participants |
| SPO2 | 96.8 mmHg STANDARD_DEVIATION 13.5 | 96.8 mmHg STANDARD_DEVIATION 12.7 | 96.8 mmHg STANDARD_DEVIATION 1.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 272 | 0 / 275 |
| other Total, other adverse events | 15 / 272 | 5 / 275 |
| serious Total, serious adverse events | 13 / 272 | 12 / 275 |
Outcome results
Primary
Number of Participants With Clinical Deterioration
Defined as the number of participants who experienced the following: both of the following: 1)Presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, 2)) decrease in O2 saturation (\<92% on room air) and/or supplemental oxygen requirement to keep O2 saturation ≥92%).
Time frame: RCT-approximately 15 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fluvoxamine | Number of Participants With Clinical Deterioration | 13 Participants |
| Placebo | Number of Participants With Clinical Deterioration | 15 Participants |