Fluvoxamine for Early Treatment of Covid-19 (Stop Covid 2)

Covid19 Clinical Trial

Official title:

Fluvoxamine for Early Treatment of Covid-19: a Fully-remote, Randomized Placebo Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04668950
• Other study ID #: 202011101
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2020
• Est. completion date: September 28, 2021

Study information

• Verified date: October 2022
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 670
• Est. completion date: September 28, 2021
• Est. primary completion date: September 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus
• COVID-19
• Covid19

Intervention

Drug:
• Fluvoxamine
Up to 200mg per day (2 capsules per day) as tolerated, for approximately 15 days
• Placebo
Will take 2 capsules per day as tolerated for approximately 15 days

Locations

Country	Name	City	State
Canada	McGill University Health Center	Montreal	Quebec
United States	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

Sponsors (4)

Lead Sponsor	Collaborator
Washington University School of Medicine	Covid-19 Early Treatment Fund, Cures Within Reach, McGill University Health Centre Department of Medicine Clinical Practice Assessment Unit

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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%).	RCT-approximately 15 days