Fluvoxamine for Early Treatment of Covid-19 (Stop Covid 2)
Condition: Covid19; Coronavirus
MeSH terms: COVID-19
Intervention: Fluvoxamine; Placebo
Intervention description: Up to 200mg per day (2 capsules per day) as tolerated, for approximately 15 days; Will take 2 capsules per day as tolerated for approximately 15 days
Intervention MeSH terms: Fluvoxamine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 670.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: fluvoxamine

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.
    

Eligibility criteria:

        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.