Fluoxetine to Reduce Intubation and Death After COVID19 Infection

NCT04377308 — Phase 4, Completed, 16 participants, University of Toledo Health Science Campus

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Registry	NCT04377308
Status	Completed
Phase	Phase 4
Study type	Interventional; non randomized, parallel, masking: none, treatment
Enrollment	16 (Actual)
Sponsor	University of Toledo Health Science Campus (Other)
Conditions	COVID-19, Cytokine Storm
Interventions	Fluoxetine (Drug)
Dates	start 2020-05-01, primary completion 2021-04-30, completion 2021-04-30, first posted 2020-05-06, last updated 2024-06-07
Locations	1 site in United States

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
Treatment As Usual	No intervention		Participants may choose to not take fluoxetine and remain in the study
Fluoxetine	Active comparator	Drug: Fluoxetine	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

Fluoxetine (Drug), also known as prozac: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration

+Outcome measures

Primary outcomes

Number of Outpatient Subject Hospitalizations [2 months]: whether the subject is hospitalized for COVID-19 symptoms
Number of Subjects Undergoing Intubation [2 months]: whether the subject is intubated for COVID-19 symptoms
Number of Patients Who Died Within 2 Months of Entry Into the Study [2 months]: Patients who died from any cause within 2 months of entry into the study.

Secondary outcomes

Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry [2 months]: Participant who achieved remission from covid with no active covid symptoms (cough, fever, shortness of breath, fatigue, muscle aches, and loss of taste and smell) from study entry
Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment [2 months]: depression score rating from 0 to 27 where higher scores indicate worse depression Scores of 10 or more meet criteria for diagnosis as a mild depressive episode
Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment [2 months]: anxiety scale with scores ranging from 0 to 21 where higher scores indicate more severe anxiety Scores of 10 or more generally indicate anxiety that might meet criteria for diagnosis as an anxiety disorder

+Eligibility

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* 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

Overall Study Exclusion Criteria :

* Unable to give informed consent and no legal representativ
* Prisoner/ institutionalized patient
* Under age 18

Exclusion from Fluoxetine Arm:

* 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

Exclusion from Blood Sample Provision:

* Pregnant
* Self-report of under 110 pounds

+Posted results

Participant flow

Milestone	Treatment As Usual	Fluoxetine
Started	4	12
Completed	4	11
Not completed	0	1

Outcome results

Number of Outpatient Subject Hospitalizations (Primary), Count of participants, Participants: Treatment As Usual 0; Fluoxetine 0
Number of Subjects Undergoing Intubation (Primary), Count of participants, Participants: Treatment As Usual 1; Fluoxetine 0
Number of Patients Who Died Within 2 Months of Entry Into the Study (Primary), Count of participants, Participants: Treatment As Usual 1; Fluoxetine 0
Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry (Secondary), Count of participants, Participants: Treatment As Usual 3; Fluoxetine 7
Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment (Secondary), Count of participants, Participants: Treatment As Usual 4; Fluoxetine 10
Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment (Secondary), Count of participants, Participants: Treatment As Usual 4; Fluoxetine 10

Adverse events

Time frame: Adverse event data was collected over up to 2 months from when each participant was enrolled by the study team.

Arm	Deaths	Serious adverse events	Other adverse events
Treatment As Usual	1/4 (25.0%)	1/4 (25.0%)	0/4 (0.0%)
Fluoxetine	0/11 (0.0%)	0/11 (0.0%)	0/11 (0.0%)

Serious adverse events by term

Term	Organ system	Treatment As Usual	Fluoxetine
Death	Respiratory, thoracic and mediastinal disorders	1/4	0/11

+Locations (1)

Facility	City	Country	Status
University of Toledo	Toledo, Ohio	United States

+Study documents

Study Protocol and Statistical Analysis Plan (PDF, 2020-05-02)