Fluoxetine to Reduce Intubation and Death After COVID19 Infection

• ClinicalTrials.gov Identifier: NCT04377308
• Recruitment Status: Completed
• First Posted: May 6, 2020
• Results First Posted: September 30, 2022
• Last Update Posted: September 30, 2022
• Sponsor: University of Toledo Health Science Campus
• Information provided by (Responsible Party): Cheryl Mccullumsmith, University of Toledo Health Science Campus

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: COVID-19; Cytokine Storm
• Intervention: Drug: Fluoxetine
• Enrollment: 16

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Treatment As Usual	Fluoxetine
Arm/Group Description	Participants may choose to not take fluoxetine and remain in the study	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: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
Period Title: Overall Study
Started	4	12
Completed	4	11
Not Completed	0	1
Reason Not Completed
Withdrawal by Subject	0	1

Baseline Characteristics

Arm/Group Title		Treatment As Usual	Fluoxetine	Total
Arm/Group Description		Participants may choose to not take fluoxetine and remain in the study	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: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration	Total of all reporting groups
Overall Number of Baseline Participants		4	11	15
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	4 participants	11 participants	15 participants
		52; (44 to 61)	46.09; (24 to 75)	47.67; (24 to 75)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	11 participants	15 participants
	Female	3 75.0%	7 63.6%	10 66.7%
	Male	1 25.0%	4 36.4%	5 33.3%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	11 participants	15 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	1 9.1%	1 6.7%
	White	4 100.0%	10 90.9%	14 93.3%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	4 participants	11 participants	15 participants
		4	11	15
Smoke Cigarettes; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	11 participants	15 participants
	Smokes cigarettes	1 25.0%	1 9.1%	2 13.3%
	Does not smoke cigarettes	3 75.0%	10 90.9%	13 86.7%

Outcome Measures

1. Primary Outcome

Title	Number of Outpatient Subject Hospitalizations
Description	whether the subject is hospitalized for COVID-19 symptoms
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

We had intended this measure for outpatients but had very few study participants who were outpatients.

Arm/Group Title	Treatment As Usual	Fluoxetine
Arm/Group Description:	Participants may choose to not take fluoxetine and remain in the study	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: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
Overall Number of Participants Analyzed	0	9
Measure Type: Count of Participants; Unit of Measure: Participants
	0	0 0.0%

2. Primary Outcome

Title	Number of Subjects Undergoing Intubation
Description	whether the subject is intubated for COVID-19 symptoms
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment As Usual	Fluoxetine
Arm/Group Description:	Participants may choose to not take fluoxetine and remain in the study	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: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
Overall Number of Participants Analyzed	4	11
Measure Type: Count of Participants; Unit of Measure: Participants
	1 25.0%	0 0.0%

3. Primary Outcome

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.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

review of charts to determine death by any cause within 2 months of entry into study

Arm/Group Title	Treatment As Usual	Fluoxetine
Arm/Group Description:	Participants may choose to not take fluoxetine and remain in the study	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: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
Overall Number of Participants Analyzed	4	11
Measure Type: Count of Participants; Unit of Measure: Participants
	1 25.0%	0 0.0%

4. Secondary Outcome

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
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment As Usual	Fluoxetine
Arm/Group Description:	Participants may choose to not take fluoxetine and remain in the study	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: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
Overall Number of Participants Analyzed	4	11
Measure Type: Count of Participants; Unit of Measure: Participants
1 or more symptom free days	3 75.0%	7 63.6%
no symptom free days	1 25.0%	4 36.4%

5. Secondary Outcome

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
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment As Usual	Fluoxetine
Arm/Group Description:	Participants may choose to not take fluoxetine and remain in the study	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: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
Overall Number of Participants Analyzed	4	10
Measure Type: Count of Participants; Unit of Measure: Participants
	4 100.0%	10 100.0%

6. Secondary Outcome

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
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment As Usual	Fluoxetine
Arm/Group Description:	Participants may choose to not take fluoxetine and remain in the study	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: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
Overall Number of Participants Analyzed	4	10
Measure Type: Count of Participants; Unit of Measure: Participants
	4 100.0%	10 100.0%

Adverse Events

Time Frame	Adverse event data was collected over up to 2 months from when each participant was enrolled by the study team.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Treatment As Usual		Fluoxetine
Arm/Group Description	Participants may choose to not take fluoxetine and remain in the study		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: Fluoxetine 20 mg to 60 mg daily given from 2 weeks to 2 months duration
All-Cause Mortality
	Treatment As Usual		Fluoxetine
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/4 (25.00%)		0/11 (0.00%)
Serious Adverse Events
	Treatment As Usual		Fluoxetine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25.00%)		0/11 (0.00%)
Respiratory, thoracic and mediastinal disorders
Death † [1]	1/4 (25.00%)	1	/11
† Indicates events were collected by systematic assessment; [1] 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.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Treatment As Usual		Fluoxetine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0.00%)		0/11 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Cheryl McCullumsmith, M.D., Ph.D.
• Organization: The University of Toledo Department of Psychiatry
• Phone: 419-383-5669
• EMail: cheryl.mccullumsmith@utoledo.edu

• Responsible Party: Cheryl Mccullumsmith, University of Toledo Health Science Campus
• ClinicalTrials.gov Identifier: NCT04377308
• Other Study ID Numbers: FRIDA COVID19
• First Submitted: April 18, 2020
• First Posted: May 6, 2020
• Results First Submitted: March 4, 2022
• Results First Posted: September 30, 2022
• Last Update Posted: September 30, 2022