Fluoxetine to Reduce Intubation and Death After COVID19 Infection

NCT04377308 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: FRIDA COVID19
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This project will test the efficacy of fluoxetine to prevent serious consequences of COVID-19 infection, especially death. Becoming sick with COVID-19 virus or any other serious respiratory condition is not fun. However, the dramatic effects of the COVID-19 pandemic on human society stem from its significant mortality, not the number of individuals who become sick. This project aims to prevent serious outcomes such as hospitalization, respiratory failure and death during the time it takes to develop vaccinations and other strategies to prevent COVID-19 infectionPoor outcomes with COVID-19 infection such as hospitalization, respiratory failure, organ failure and death are associated with a dysfunctional exaggerated immune response, called a cytokine storm, that is triggered by Interleukin-6 expression (IL-6) and seems to occur around day 5 to 7 of symptoms. Fluoxetine has extraordinarily strong evidence in its action as a blocker of IL-6 and cytokine storms in both animal models of infection and in human illness such as rheumatoid arthritis and others. This action of fluoxetine is an entirely separate pathway than the serotonergic pathway that allows fluoxetine to act as an antidepressant. This pathway has been demonstrated in cell culture, in animal models, in human illness and by novel bioinformatics analyses of protein transcripts to be relatively unique for fluoxetine and appears to be a novel pathway. This project aims to inhibit the increase in IL-6 expression and thereby prevent the cytokine storm that causes poor outcomes. Patients who have tested positive or are presumptively positive for COVID-19 will be entered into the study and given the option to start the medication fluoxetine, which is demonstrated to prevent IL-6 surges in infectious and inflammatory conditions. Participants will be monitored daily for COVID-19 symptoms and weekly for side effects and tolerance of fluoxetine. A subset of patients will have blood drawn weekly and stored to monitor IL-6 and other cytokine levels at a later date. This project aims to reduce the serious outcomes of COVID-19 infection by preventing or inhibiting the cytokine storm associated with organ failure, respiratory failure and death.

Conditions

COVID-19; Cytokine Storm

Keywords

IL-6; fluoxetine; cytokine storm; NF-KB; COVID-19

Outcome Measures

Primary Outcomes (3)

• Number of Outpatient Subject Hospitalizations

  whether the subject is hospitalized for COVID-19 symptoms

  2 months

• Number of Subjects Undergoing Intubation

  whether the subject is intubated for COVID-19 symptoms

  2 months

• Number of Patients Who Died Within 2 Months of Entry Into the Study

  Patients who died from any cause within 2 months of entry into the study.

  2 months

Secondary Outcomes (3)

• Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry

  2 months

• Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment

  2 months

• Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment

  2 months

Study Arms (2)

Treatment As Usual

NO INTERVENTION

Participants may choose to not take fluoxetine and remain in the study

Fluoxetine

ACTIVE COMPARATOR

Participants will take fluoxetine 20 mg initially, increasing as tolerated to a maximum of 60 mg until symptoms abate, then will be tapered by 20 mg per week off the fluoxetine Participants will be on fluoxetine for 2 weeks to 2 months depending on symptom duration

Drug: Fluoxetine

Interventions

Fluoxetine DRUG

Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration

Also known as: prozac

Fluoxetine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 and above, able to give informed consent or with legally authorized representative
• COVID-19 test positive or presumptive positive awaiting COVID testing or results by following criteria: fever, cough and shortness of breath or presumptive positive by one of these 3 criteria (fever, cough or shortness of breath) and known exposure to COVID-19 positive individual in past 2 weeks

You may not qualify if:

• Unable to give informed consent and no legal representativ
• Prisoner/ institutionalized patient
• Under age 18
• Active bleeding requiring blood products
• Bipolar disorder not on mood stabilizing medication\*
• Known allergy or hypersensitivity to fluoxetine
• Currently taking the following medications : MAO I, pimozide, thioridine
• Currently taking hydroxychloroquine
• Pregnant or breastfeeding
• For hospitalized patients : QTc greater than 500 ms
• \*Hospitalized patient may be on hydroxychloroquine if QTc\<500 and the primary attending approves
• Pregnant
• Self-report of under 110 pounds

Sponsors & Collaborators

• University of Toledo Health Science Campus: lead

Study Sites (1)

University of Toledo

Toledo, Ohio, 43614, United States

Location

MeSH Terms

Conditions

COVID-19; Cytokine Release Syndrome

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Cheryl McCullumsmith, M.D., Ph.D.
• Organization: The University of Toledo Department of Psychiatry

cheryl.mccullumsmith@utoledo.edu

419-383-5669

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair, Department of Psychiatry

Model Details: All patients who enter the study will be monitored daily for symptoms of COVID-19. Patients may choose to take fluoxetine or to have treatment as usual. Patients may also choose to have blood drawn and stored for a future analysis of cytokines.

Study Record Dates

• First Submitted: April 18, 2020
• First Posted: May 6, 2020
• Study Start: May 1, 2020
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: June 7, 2024
• Results First Posted: September 30, 2022

Record last verified: 2024-06

Locations

US (1)