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

NCT ID: NCT04668950

Last Updated: 2022-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 670 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-22
• Study Completion Date: 2021-09-28

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.

Conditions

Covid19; Coronavirus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Fluvoxamine

Intervention Type: DRUG

Up to 200mg per day (2 capsules per day) as tolerated, for approximately 15 days

Placebo

Start placebo one capsule, twice daily. May reduce dose for tolerability reasons. Will be followed in RCT for approximately 15 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Will take 2 capsules per day as tolerated for approximately 15 days

Interventions

Fluvoxamine

Up to 200mg per day (2 capsules per day) as tolerated, for approximately 15 days

Intervention Type: DRUG

Placebo

Will take 2 capsules per day as tolerated for approximately 15 days

Intervention Type: DRUG

Other Intervention Names

Luvox

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.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Covid-19 Early Treatment Fund

OTHER

Sponsor Role: collaborator

McGill University

OTHER

Sponsor Role: collaborator

Cures Within Reach

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Eric Lenze

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Northwestern University

Chicago, Illinois, United States

Washington University School of Medicine

St 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

Countries

United States; Canada

References

Reiersen AM, Mattar C, Bender Ignacio RA, Boulware DR, Lee TC, Hess R, Lankowski AJ, McDonald EG, Miller JP, Powderly WG, Pullen MF, Rado JT, Rich MW, Schiffer JT, Schweiger J, Spivak AM, Stevens A, Vigod SN, Agarwal P, Yang L, Yingling M, Gettinger TR, Zorumski CF, Lenze EJ. The STOP COVID 2 Study: Fluvoxamine vs Placebo for Outpatients With Symptomatic COVID-19, a Fully Remote Randomized Controlled Trial. Open Forum Infect Dis. 2023 Aug 8;10(8):ofad419. doi: 10.1093/ofid/ofad419. eCollection 2023 Aug.

Reference Type: DERIVED

PMID: 37622035 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

202011101

Identifier Type: -

Identifier Source: org_study_id