COVID-19Phase 4NCT04377308
Fluoxetine to Reduce Intubation and Death After COVID19 Infection
A Phase 4 study testing Fluoxetine in people with COVID-19 and Cytokine Storm, run by University of Toledo Health Science Campus at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- COVID-19, Cytokine Storm
- What is being tested?
- Fluoxetine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2020to 30 Apr 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Fluoxetine
- Keywords
- IL-6, fluoxetine, cytokine storm, NF-KB, COVID-19
- Medical subject headings
- COVID-19, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluoxetineDrug
Also called prozac
Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Fluoxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Outpatient Subject Hospitalizations
whether the subject is hospitalized for COVID-19 symptoms
Measured: 2 months
Number of Subjects Undergoing Intubation
whether the subject is intubated for COVID-19 symptoms
Measured: 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.
Measured: 2 months
Secondary outcomes (3)
Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry
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
Measured: 2 months
Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment
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
Measured: 2 months
Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment
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
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2020
- Study start1 May 2020
- Primary completion30 Apr 2021
- Study completion30 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Toledo Health Science Campus
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cheryl Mccullumsmith, University of Toledo Health Science Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04377308
- Sponsor's protocol ID
- FRIDA COVID19
- Status last verified
- Jun 2024
- First submitted
- 18 Apr 2020
- Last updated
- 7 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluoxetine to Reduce Intubation and Death After COVID19 Infection
- ClinicalTrials.gov ID
- NCT04377308
- Acronym / sponsor ID
- FRIDA COVID19
- Conditions
- COVID-19, Cytokine Storm
- Keywords
- IL-6, fluoxetine, cytokine storm, NF-KB, COVID-19
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of Toledo Health Science CampusUniversity, hospital or other
- Study start
- 1 May 2020 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 30 Apr 2021 (actual)
- First posted
- 6 May 2020 (actual)
- Results
- Posted 30 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Treatment As Usual | No intervention | –Participants may choose to not take fluoxetine and remain in the study |
| Fluoxetine | Active comparator | Drug: FluoxetineParticipants 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
- Unable to give informed consent and no legal representativ
- Prisoner/ institutionalized patient
- Under age 18
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FluoxetineAlso: prozacFluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration | Drug | Fluoxetine |
Primary outcome
Number of Outpatient Subject Hospitalizations
Time frame: 2 months
whether the subject is hospitalized for COVID-19 symptoms
Number of Subjects Undergoing Intubation
Time frame: 2 months
whether the subject is intubated for COVID-19 symptoms
Number of Patients Who Died Within 2 Months of Entry Into the Study
Time frame: 2 months
Patients who died from any cause within 2 months of entry into the study.
3 secondary outcomes
Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry
Time frame: 2 months
Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment
Time frame: 2 months
Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment
Time frame: 2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fluoxetine in people with COVID-19 and Cytokine Storm, run by University of Toledo Health Science Campus at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Outpatient Subject Hospitalizations (time frame: 2 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2024.