Coronavirus, COVID 19
Conditions
Keywords
COVID 19, 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. Only residents of Missouri and Illinois may participate.
Detailed description
We will consent approximately 152 participants, age 18 and older, who have tested tested positive for COVID-19 and are currently experiencing mild symptoms. 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 a pregnancy test (for females of childbearing age not using contraception), an oxygen saturation monitor, blood pressure monitor, and thermometer. Once the study team has finalized the screening process, the participant will begin taking the study medication. 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 100mg of fluvoxamine or placebo by mouth three times a day for a daily total of 300mg. They will continue this dose for approximately 15 days. Depending on tolerability, the dose may be adjusted. Participants will also complete short 10-15 minute assessments daily to assess symptoms, results of self-monitoring (including oxygen level, blood pressure, and temperature) and any adverse events. Open-label Phase: After completing the randomization phase, participants will then participate in an open-label phase (participant will definitely receive fluvoxamine) that will last up to 15 days. Those randomized to placebo will have the opportunity to try fluvoxamine during this time. Those randomized to fluvoxamine will continue this medication while slowly decreasing the drug. The participant may opt out of this phase. The dosage during this time will be 50-100mg two times daily until discontinuing the drug. Follow-up Phase: We will follow participants for approximately 30 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
Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 300mg per day (3 capsules per day) as tolerated.
DRUGPlacebo
Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 3 capsules per day as tolerated.
Sponsors
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
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. men and woman age 18 and older; 2. Not hospitalized; 3. Has recently tested SARS-CoV-2 (COVID-19 virus) positive. 4. Currently symptomatic with one or more of one or more of the following symptoms: fever, cough, myalgia, mild dyspnea, diarrhea, vomiting, anosmia (inability to smell), ageusia (inability to taste), sore throat. 5. Able to provide informed consent.
Exclusion criteria
1. Illness severe enough to require hospitalization or already meeting study's primary endpoint for clinical worsening. 2. Unstable medical comorbidities including, but not limited to: Severe underlying lung disease (COPD on home oxygen, interstitial lung disease, pulmonary hypertension), decompensated cirrhosis, Congestive heart failure (stage 3 or 4 per patient report and/or medical records). 3. Immunocompromised (solid organ transplant, BMT, AIDS, on biologics and/or high dose steroids (\>20mg prednisone per day) 4. Unable to provide informed consent (eg moderate-severe dementia diagnosis) 5. Unable to perform the study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Met Clinical Worsening | RCT (approximately 15 days) | Clinical worsening is defined meeting both of the following: (1) presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, plus (2) decrease in O2 saturation (\<92%) on room air and/or supplemental oxygen requirement in order to keep O2 saturation \>92%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Deterioration on a Likert-type Scale (0-6) | RCT (approximately 15 days) | (0) none; (1) moderate severity of illness as defined by O2 saturation \<92% but no supplemental oxygen requirement; (2) O2 saturation plus supplemental oxygen requirement; (3) O2 saturation \<92% plus hospitalization (related to dyspnea/hypoxia); (4) the above, plus ventilator support requirement; (5) the above, plus ventilator support for at least 3 days; (6) death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluvoxamine Start fluvoxamine 100mg capsules, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in the RCT for approximately 15 days.
Fluvoxamine: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 300mg per day (3 capsules per day) as tolerated. | 80 |
| Placebo Start placebo one capsule, three times daily. May reduce dose (or start at reduced dose) for tolerability reasons. Will be followed in RCT for approximately 15 days.
Placebo: Randomized to either fluvoxamine or placebo for approximately 15 days. Will take up to 3 capsules per day as tolerated. | 72 |
| Total | 152 |
Baseline characteristics
| Characteristic | Total | Fluvoxamine | Placebo |
|---|---|---|---|
| Age, Continuous | 46 years | 46 years | 45 years |
| Body mass index category Normal (18.5-24.9) | 21 Participants | 14 Participants | 7 Participants |
| Body mass index category Obese (≥30) | 85 Participants | 43 Participants | 42 Participants |
| Body mass index category Overweight (25-29.9) | 44 Participants | 22 Participants | 22 Participants |
| Body mass index category Underweight (<18.5) | 2 Participants | 1 Participants | 1 Participants |
| Co-existing conditions Anxiety | 6 Participants | 5 Participants | 1 Participants |
| Co-existing conditions Arthritis | 7 Participants | 4 Participants | 3 Participants |
| Co-existing conditions Asthma | 26 Participants | 17 Participants | 9 Participants |
| Co-existing conditions Depression | 5 Participants | 1 Participants | 4 Participants |
| Co-existing conditions Diabetes | 17 Participants | 9 Participants | 8 Participants |
| Co-existing conditions High cholesterol | 14 Participants | 7 Participants | 7 Participants |
| Co-existing conditions Hypertension | 30 Participants | 15 Participants | 15 Participants |
| Co-existing conditions Hyperthyroidism | 12 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 141 Participants | 75 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 2 Participants | 4 Participants |
| Most severe COVID 19 symptom at baseline Body aches | 22 Participants | 9 Participants | 13 Participants |
| Most severe COVID 19 symptom at baseline Chills | 9 Participants | 3 Participants | 6 Participants |
| Most severe COVID 19 symptom at baseline Cough | 10 Participants | 9 Participants | 1 Participants |
| Most severe COVID 19 symptom at baseline Fatigue | 35 Participants | 17 Participants | 18 Participants |
| Most severe COVID 19 symptom at baseline Loss of appetite | 11 Participants | 3 Participants | 8 Participants |
| Most severe COVID 19 symptom at baseline Loss of sense of smell | 44 Participants | 26 Participants | 18 Participants |
| Most severe COVID 19 symptom at baseline Loss of taste | 4 Participants | 2 Participants | 2 Participants |
| Most severe COVID 19 symptom at baseline Nausea | 2 Participants | 1 Participants | 1 Participants |
| Most severe COVID 19 symptom at baseline Shortness of breath | 3 Participants | 2 Participants | 1 Participants |
| Most severe COVID 19 symptom at baseline Subjective fever | 12 Participants | 8 Participants | 4 Participants |
| Oxygen saturation | 97 percentage of oxygen saturation | 97 percentage of oxygen saturation | 97 percentage of oxygen saturation |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 18 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 106 Participants | 56 Participants | 50 Participants |
| Sex: Female, Male Female | 109 Participants | 56 Participants | 53 Participants |
| Sex: Female, Male Male | 43 Participants | 24 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 0 / 72 |
| other Total, other adverse events | 13 / 80 | 28 / 72 |
| serious Total, serious adverse events | 1 / 80 | 6 / 72 |
Outcome results
Primary
Number of Participants Who Met Clinical Worsening
Clinical worsening is defined meeting both of the following: (1) presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, plus (2) decrease in O2 saturation (\<92%) on room air and/or supplemental oxygen requirement in order to keep O2 saturation \>92%.
Time frame: RCT (approximately 15 days)
Population: The primary and secondary end points were measured using participants' self-reported responses on twice-daily surveys during the 15 days after randomization that were corroborated by research staff with phone contact.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fluvoxamine | Number of Participants Who Met Clinical Worsening | 0 Participants |
| Placebo | Number of Participants Who Met Clinical Worsening | 6 Participants |
Secondary
Clinical Deterioration on a Likert-type Scale (0-6)
(0) none; (1) moderate severity of illness as defined by O2 saturation \<92% but no supplemental oxygen requirement; (2) O2 saturation plus supplemental oxygen requirement; (3) O2 saturation \<92% plus hospitalization (related to dyspnea/hypoxia); (4) the above, plus ventilator support requirement; (5) the above, plus ventilator support for at least 3 days; (6) death.
Time frame: RCT (approximately 15 days)
Population: The primary and secondary end points were measured using participants' self-reported responses on twice-daily surveys during the 15 days after randomization that were corroborated by research staff with phone contact.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluvoxamine | Clinical Deterioration on a Likert-type Scale (0-6) | 2, O2 saturation plus supplemental oxygen requirement | 0 Participants |
| Fluvoxamine | Clinical Deterioration on a Likert-type Scale (0-6) | 4, the above, plus ventilator support requirement; | 0 Participants |
| Fluvoxamine | Clinical Deterioration on a Likert-type Scale (0-6) | 1, shortness of breath and oxygen saturation less than 92% but no supplemental oxygen needed | 0 Participants |
| Fluvoxamine | Clinical Deterioration on a Likert-type Scale (0-6) | 5, oxygen < 92%, + supplemental O2, hospitalized related to dyspnea/hypoxia + ventilator 3 days | 0 Participants |
| Fluvoxamine | Clinical Deterioration on a Likert-type Scale (0-6) | 3, oxygen saturation less than 92% + supplemental O2 and hospitalized related to dyspnea or hypoxia | 0 Participants |
| Fluvoxamine | Clinical Deterioration on a Likert-type Scale (0-6) | 6, Death | 0 Participants |
| Fluvoxamine | Clinical Deterioration on a Likert-type Scale (0-6) | 0 (none) | 80 Participants |
| Placebo | Clinical Deterioration on a Likert-type Scale (0-6) | 6, Death | 0 Participants |
| Placebo | Clinical Deterioration on a Likert-type Scale (0-6) | 0 (none) | 66 Participants |
| Placebo | Clinical Deterioration on a Likert-type Scale (0-6) | 1, shortness of breath and oxygen saturation less than 92% but no supplemental oxygen needed | 2 Participants |
| Placebo | Clinical Deterioration on a Likert-type Scale (0-6) | 2, O2 saturation plus supplemental oxygen requirement | 0 Participants |
| Placebo | Clinical Deterioration on a Likert-type Scale (0-6) | 3, oxygen saturation less than 92% + supplemental O2 and hospitalized related to dyspnea or hypoxia | 3 Participants |
| Placebo | Clinical Deterioration on a Likert-type Scale (0-6) | 4, the above, plus ventilator support requirement; | 0 Participants |
| Placebo | Clinical Deterioration on a Likert-type Scale (0-6) | 5, oxygen < 92%, + supplemental O2, hospitalized related to dyspnea/hypoxia + ventilator 3 days | 1 Participants |