Clinical trial NCT04377308: Fluoxetine to Reduce Intubation and Death After COVID19 Infection
Official title: Fluoxetine to Reduce Intubation and Death After COVID19 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COVID-19
Cytokine Storm
Keywords: IL-6
fluoxetine
cytokine storm
NF-KB
COVID-19
Lead sponsor: University of Toledo
Sponsor class: OTHER
First posted: 2020-05-06
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Outpatient Subject Hospitalizations
timeFrame: 2 months
measure: Number of Subjects Undergoing Intubation
timeFrame: 2 months
measure: Number of Patients Who Died Within 2 Months of Entry Into the Study
timeFrame: 2 months
Secondary outcomes:
measure: Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry
timeFrame: 2 months
measure: Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment
timeFrame: 2 months
measure: Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment
timeFrame: 2 months
Other outcomes:
Locations:
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
Study officials:
References: