{"protocolSection":{"identificationModule":{"nctId":"NCT04377308","orgStudyIdInfo":{"id":"FRIDA COVID19"},"organization":{"fullName":"University of Toledo","class":"OTHER"},"briefTitle":"Fluoxetine to Reduce Intubation and Death After COVID19 Infection","officialTitle":"Fluoxetine to Reduce Intubation and Death After COVID19 Infection"},"statusModule":{"statusVerifiedDate":"2024-06","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2020-05-01","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2021-04-30","type":"ACTUAL"},"completionDateStruct":{"date":"2021-04-30","type":"ACTUAL"},"studyFirstSubmitDate":"2020-04-18","studyFirstSubmitQcDate":"2020-05-04","studyFirstPostDateStruct":{"date":"2020-05-06","type":"ACTUAL"},"resultsFirstSubmitDate":"2022-03-04","resultsFirstSubmitQcDate":"2022-09-17","resultsFirstPostDateStruct":{"date":"2022-09-30","type":"ACTUAL"},"lastUpdateSubmitDate":"2024-06-05","lastUpdatePostDateStruct":{"date":"2024-06-07","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Cheryl Mccullumsmith","investigatorTitle":"Professor and Chair, Department of Psychiatry","investigatorAffiliation":"University of Toledo Health Science Campus"},"leadSponsor":{"name":"University of Toledo Health Science Campus","class":"OTHER"}},"oversightModule":{"oversightHasDmc":true,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false,"isUsExport":false},"descriptionModule":{"briefSummary":"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.\n\nThis 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."},"conditionsModule":{"conditions":["COVID-19","Cytokine Storm"],"keywords":["IL-6","fluoxetine","cytokine storm","NF-KB","COVID-19"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"NON_RANDOMIZED","interventionModel":"PARALLEL","interventionModelDescription":"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.","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"NONE"}},"enrollmentInfo":{"count":16,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Treatment As Usual","type":"NO_INTERVENTION","description":"Participants may choose to not take fluoxetine and remain in the study"},{"label":"Fluoxetine","type":"ACTIVE_COMPARATOR","description":"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","interventionNames":["Drug: Fluoxetine"]}],"interventions":[{"type":"DRUG","name":"Fluoxetine","description":"Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration","armGroupLabels":["Fluoxetine"],"otherNames":["prozac"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Number of Outpatient Subject Hospitalizations","description":"whether the subject is hospitalized for COVID-19 symptoms","timeFrame":"2 months"},{"measure":"Number of Subjects Undergoing Intubation","description":"whether the subject is intubated for COVID-19 symptoms","timeFrame":"2 months"},{"measure":"Number of Patients Who Died Within 2 Months of Entry Into the Study","description":"Patients who died from any cause within 2 months of entry into the study.","timeFrame":"2 months"}],"secondaryOutcomes":[{"measure":"Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry","description":"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","timeFrame":"2 months"},{"measure":"Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment","description":"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","timeFrame":"2 months"},{"measure":"Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment","description":"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","timeFrame":"2 months"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Patients aged 18 and above, able to give informed consent or with legally authorized representative\n* 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\n\nOverall Study Exclusion Criteria :\n\n* Unable to give informed consent and no legal representativ\n* Prisoner/ institutionalized patient\n* Under age 18\n\nExclusion from Fluoxetine Arm:\n\n* Active bleeding requiring blood products\n* Bipolar disorder not on mood stabilizing medication\\*\n* Known allergy or hypersensitivity to fluoxetine\n* Currently taking the following medications : MAO I, pimozide, thioridine\n* Currently taking hydroxychloroquine\n* Pregnant or breastfeeding\n* For hospitalized patients : QTc greater than 500 ms\n* \\*Hospitalized patient may be on hydroxychloroquine if QTc\\<500 and the primary attending approves\n\nExclusion from Blood Sample Provision:\n\n* Pregnant\n* Self-report of under 110 pounds","healthyVolunteers":true,"sex":"ALL","minimumAge":"18 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"locations":[{"facility":"University of Toledo","city":"Toledo","state":"Ohio","zip":"43614","country":"United States","geoPoint":{"lat":41.66394,"lon":-83.55521}}]}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Treatment As Usual","description":"Participants may choose to not take fluoxetine and remain in the study"},{"id":"FG001","title":"Fluoxetine","description":"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\n\nFluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"4"},{"groupId":"FG001","numSubjects":"12"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"4"},{"groupId":"FG001","numSubjects":"11"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"1"}]}],"dropWithdraws":[{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"1"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Treatment As Usual","description":"Participants may choose to not take fluoxetine and remain in the study"},{"id":"BG001","title":"Fluoxetine","description":"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\n\nFluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"11"},{"groupId":"BG002","value":"15"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"FULL_RANGE","unitOfMeasure":"Years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"52","lowerLimit":"44","upperLimit":"61"},{"groupId":"BG001","value":"46.09","lowerLimit":"24","upperLimit":"75"},{"groupId":"BG002","value":"47.67","lowerLimit":"24","upperLimit":"75"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"3"},{"groupId":"BG001","value":"7"},{"groupId":"BG002","value":"10"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"4"},{"groupId":"BG002","value":"5"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"1"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"10"},{"groupId":"BG002","value":"14"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"11"},{"groupId":"BG002","value":"15"}]}]}]},{"title":"Smoke Cigarettes","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Smokes cigarettes","measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"2"}]},{"title":"Does not smoke cigarettes","measurements":[{"groupId":"BG000","value":"3"},{"groupId":"BG001","value":"10"},{"groupId":"BG002","value":"13"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Number of Outpatient Subject Hospitalizations","description":"whether the subject is hospitalized for COVID-19 symptoms","populationDescription":"We had intended this measure for outpatients but had very few study participants who were outpatients.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"2 months","groups":[{"id":"OG000","title":"Treatment As Usual","description":"Participants may choose to not take fluoxetine and remain in the study"},{"id":"OG001","title":"Fluoxetine","description":"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\n\nFluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"9"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"}]}]}]},{"type":"PRIMARY","title":"Number of Subjects Undergoing Intubation","description":"whether the subject is intubated for COVID-19 symptoms","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"2 months","groups":[{"id":"OG000","title":"Treatment As Usual","description":"Participants may choose to not take fluoxetine and remain in the study"},{"id":"OG001","title":"Fluoxetine","description":"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\n\nFluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"11"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"0"}]}]}]},{"type":"PRIMARY","title":"Number of Patients Who Died Within 2 Months of Entry Into the Study","description":"Patients who died from any cause within 2 months of entry into the study.","populationDescription":"review of charts to determine death by any cause within 2 months of entry into study","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"2 months","groups":[{"id":"OG000","title":"Treatment As Usual","description":"Participants may choose to not take fluoxetine and remain in the study"},{"id":"OG001","title":"Fluoxetine","description":"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\n\nFluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"11"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"0"}]}]}]},{"type":"SECONDARY","title":"Participants With 1 or More Symptom Free Day With no COVID Primary Symptoms During 2 Months After Study Entry","description":"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","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"2 months","groups":[{"id":"OG000","title":"Treatment As Usual","description":"Participants may choose to not take fluoxetine and remain in the study"},{"id":"OG001","title":"Fluoxetine","description":"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\n\nFluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"11"}]}],"classes":[{"categories":[{"title":"1 or more symptom free days","measurements":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"7"}]},{"title":"no symptom free days","measurements":[{"groupId":"OG000","value":"1"},{"groupId":"OG001","value":"4"}]}]}]},{"type":"SECONDARY","title":"Participants With Patient Health Questionnaire (PHQ) -9 Score Below 10 After Baseline Assessment","description":"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","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"2 months","groups":[{"id":"OG000","title":"Treatment As Usual","description":"Participants may choose to not take fluoxetine and remain in the study"},{"id":"OG001","title":"Fluoxetine","description":"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\n\nFluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"10"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"10"}]}]}]},{"type":"SECONDARY","title":"Participants With Generalized Anxiety Disorder (GAD) -7 Scale Score Below 10 After Baseline Assessment","description":"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","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"2 months","groups":[{"id":"OG000","title":"Treatment As Usual","description":"Participants may choose to not take fluoxetine and remain in the study"},{"id":"OG001","title":"Fluoxetine","description":"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\n\nFluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"10"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"10"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"0","timeFrame":"Adverse event data was collected over up to 2 months from when each participant was enrolled by the study team.","eventGroups":[{"id":"EG000","title":"Treatment As Usual","description":"Participants may choose to not take fluoxetine and remain in the study","deathsNumAffected":1,"deathsNumAtRisk":4,"seriousNumAffected":1,"seriousNumAtRisk":4,"otherNumAffected":0,"otherNumAtRisk":4},{"id":"EG001","title":"Fluoxetine","description":"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\n\nFluoxetine: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration","deathsNumAffected":0,"deathsNumAtRisk":11,"seriousNumAffected":0,"seriousNumAtRisk":11,"otherNumAffected":0,"otherNumAtRisk":11}],"seriousEvents":[{"term":"Death","organSystem":"Respiratory, thoracic and mediastinal disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","notes":"Patient went in to acute respiratory failure secondary to COVID-19 PNA, coded, was emergently intubated and died after attempts to resuscitate. Patient was in the control arm of the study and did not receive the study drug.","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":4},{"groupId":"EG001","numAtRisk":11}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":true},"pointOfContact":{"title":"Cheryl McCullumsmith, M.D., Ph.D.","organization":"The University of Toledo Department of Psychiatry","email":"cheryl.mccullumsmith@utoledo.edu","phone":"419-383-5669"}}},"documentSection":{"largeDocumentModule":{"largeDocs":[{"typeAbbrev":"Prot_SAP","hasProtocol":true,"hasSap":true,"hasIcf":false,"label":"Study Protocol and Statistical Analysis Plan","date":"2020-05-02","uploadDate":"2022-09-17T12:16","filename":"Prot_SAP_002.pdf","size":619834}]}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13","submissionTracking":{"firstMcpInfo":{"postDateStruct":{"date":"2022-03-16","type":"ACTUAL"}}}},"conditionBrowseModule":{"meshes":[{"id":"D000086382","term":"COVID-19"},{"id":"D000080424","term":"Cytokine Release Syndrome"}],"ancestors":[{"id":"D011024","term":"Pneumonia, Viral"},{"id":"D011014","term":"Pneumonia"},{"id":"D012141","term":"Respiratory Tract Infections"},{"id":"D007239","term":"Infections"},{"id":"D014777","term":"Virus Diseases"},{"id":"D018352","term":"Coronavirus Infections"},{"id":"D003333","term":"Coronaviridae Infections"},{"id":"D030341","term":"Nidovirales Infections"},{"id":"D012327","term":"RNA Virus Infections"},{"id":"D008171","term":"Lung Diseases"},{"id":"D012140","term":"Respiratory Tract Diseases"},{"id":"D018746","term":"Systemic Inflammatory Response Syndrome"},{"id":"D007249","term":"Inflammation"},{"id":"D010335","term":"Pathologic Processes"},{"id":"D013568","term":"Pathological Conditions, Signs and Symptoms"},{"id":"D012769","term":"Shock"}]},"interventionBrowseModule":{"meshes":[{"id":"D005473","term":"Fluoxetine"}],"ancestors":[{"id":"D011437","term":"Propylamines"},{"id":"D000588","term":"Amines"},{"id":"D009930","term":"Organic Chemicals"}]}},"hasResults":true}