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.
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.
Drug: Fluvoxamine
Up to 200mg per day (2 capsules per day) as tolerated, for approximately 15 days
Other Name: Luvox
Drug: Placebo
Will take 2 capsules per day as tolerated for approximately 15 days
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.
Northwestern University
Chicago, Illinois, United States
Washington University School of Medicine
Saint Louis, Missouri, United States
University of Utah
Salt Lake City, Utah, United States
Fred Hutchinson
Seattle, Washington, United States
McGill University Health Center
Montreal, Quebec, Canada