Trial Outcomes & Findings for Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial (NCT NCT03638908)
NCT ID: NCT03638908
Last Updated: 2020-06-26
Results Overview
Change in PVR between baseline and follow-up will be utilized. PVR is calculated as \[(Pulmonary Artery mean - wedge) / Fick Cardiac Output\]. Fick CO will be used in computing PVR over thermodilution because Fick appears to have greater precision (but not accuracy). The calculation of PVR above is measured in woods unit. Change is derived by getting the difference between baseline and week 24 PVR (Week 24 minus Baseline). mean is then computed by getting the average of the change
COMPLETED
PHASE2
8 participants
Baseline and Week 24
2020-06-26
Participant Flow
Subjects were recruited solely from the clinic from November 2013 to November 2016
This was an open label study and all subjects were assigned to receive Fluoxetine.
Participant milestones
| Measure |
Fluoxetine
Dosing will be
* Week 1-4: 20 mg daily
* Week 5-8: 40 mg daily
* Week 9-12: 60 mg daily
* Week 13-24: 80 mg daily
Fluoxetine
|
|---|---|
|
Overall Study
STARTED
|
8
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial
Baseline characteristics by cohort
| Measure |
Fluoxetine
n=8 Participants
Dosing will be
* Week 1-4: 20 mg daily
* Week 5-8: 40 mg daily
* Week 9-12: 60 mg daily
* Week 13-24: 80 mg daily
Fluoxetine
|
|---|---|
|
Age, Continuous
|
44.5 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race/ethnicity · White non-hispanic
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race/ethnicity · Hispanic
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race/ethnicity · African American
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 24Population: 6 out of the 8 subjects enrolled had complete- baseline and week 24- data for analysis
Change in PVR between baseline and follow-up will be utilized. PVR is calculated as \[(Pulmonary Artery mean - wedge) / Fick Cardiac Output\]. Fick CO will be used in computing PVR over thermodilution because Fick appears to have greater precision (but not accuracy). The calculation of PVR above is measured in woods unit. Change is derived by getting the difference between baseline and week 24 PVR (Week 24 minus Baseline). mean is then computed by getting the average of the change
Outcome measures
| Measure |
Fluoxetine
n=6 Participants
Dosing will be
* Week 1-4: 20 mg daily
* Week 5-8: 40 mg daily
* Week 9-12: 60 mg daily
* Week 13-24: 80 mg daily
|
Fluoxetine- Week 24
subject data at week 24
|
|---|---|---|
|
Pulmonary Vascular Resistance (PVR)
|
6.7 woods unit
Standard Deviation 2.7
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: unable to adequately analyze outcome as there were several missing data- values provided below are not meaningful.
Urine for spot urine 5-HIAA will be collected at baseline and Week 24. Subjects will be on diet restriction 72 hours prior to urine collection. Sample will be the first morning urine on the visit day. Sample will be brought to site and then sent to affiliate outside laboratory for processing. 5HIAA results are expressed as a ratio to creatinine excretion in the unit "mg/g creatinine" Change 5-HIAA is derived by getting the difference between baseline and week 24 5HIAA results (Week 24 minus Baseline). mean is then computed by getting the average of the change
Outcome measures
| Measure |
Fluoxetine
n=5 Participants
Dosing will be
* Week 1-4: 20 mg daily
* Week 5-8: 40 mg daily
* Week 9-12: 60 mg daily
* Week 13-24: 80 mg daily
|
Fluoxetine- Week 24
subject data at week 24
|
|---|---|---|
|
5-HIAA (HYDROXYINDOLE ACETIC ACID) Level
|
0.375 mg/g CRT
Standard Deviation 0.182
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Week 24Population: unable to analyze outcome as this sub-study was dependent on obtaining additional funding- samples were collected but not processed to provide result
About 20ml blood will be obtained for plasma and serum at Baseline and Week 24. This will be placed in a red-top tube (serum, at least 1 ml) and blue-top tube. For the plasma tests, a plasma volume of 750 microL is required. Samples will be sent together, as a batch of 50 is required, on dry ice via overnight courier. Plasma will be obtained by drawing blood into a blue-top citrated tube, inverting the tube 6 times, and then centrifuging at 2000g for 10 minutes. The platelet poor plasma will be drawn off, and then re-centrifuged for 10 minutes before freezing.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 24Population: 6 out of total enrolled had complete data for analysis
Exercise capacity will be measure using the 6-minute walk test. Data collected at baseline and 24 were analyzed. The test will follow the ATS guidelines for 6MWT at all time.
Outcome measures
| Measure |
Fluoxetine
n=6 Participants
Dosing will be
* Week 1-4: 20 mg daily
* Week 5-8: 40 mg daily
* Week 9-12: 60 mg daily
* Week 13-24: 80 mg daily
|
Fluoxetine- Week 24
n=6 Participants
subject data at week 24
|
|---|---|---|
|
Exercise Capacity
|
380 meters
Standard Deviation 80.7
|
393 meters
Standard Deviation 78.6
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 24Population: analysis was not done as study primary endpoint was not met- since primary endpoint was not met, no further analyses were completed
Functional class will be measured using the WHO functional class assessment. This is graded from WHO FC I to FC IV. Assessment will be completed by an investigator on the study at every visit.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and Week 24.Population: 7 subjects of the total enrolled were included in the descriptive analysis. 1 subject did not complete the study
Patient reported outcome will be assessed using the Quick Inventory of Depressive Symptomatology (16-Item) (Self-Report) (QIDS-SR16) completed at baseline, week 12 and Week 24; baseline and week 24 reported. Each question is scored from minimum of 0 to a maximum of 3; total score ranges from 0 to 42. With zero being better outcome and 42 being severe outcome
Outcome measures
| Measure |
Fluoxetine
n=7 Participants
Dosing will be
* Week 1-4: 20 mg daily
* Week 5-8: 40 mg daily
* Week 9-12: 60 mg daily
* Week 13-24: 80 mg daily
|
Fluoxetine- Week 24
n=7 Participants
subject data at week 24
|
|---|---|---|
|
Quick Inventory of Depressive Symptomatology
|
4.7 score on a scale
Standard Deviation 2.3
|
4.3 score on a scale
Standard Deviation 3.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baselinePopulation: analysis was not done as study primary endpoint was not met- since primary endpoint was not met, no further analyses were completed
PGIS questionnaire will be administered for global assessment of severity. This questionnaire is categorical and measures outcome from "none" being best outcome to "severe" being the worst outcome
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 12 and Week 24.Population: analysis was not done as study primary endpoint was not met- since primary endpoint was not met, no further analyses were completed
Global assessment of severity will be determined using Clinician global impression of severity - symptoms (CGIS). This questionnaire is categorical and measures outcome from "none" being best outcome to "severe" being the worst outcome
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline, Week 12 and Week 24.Population: analysis was not done as study primary endpoint was not met- since primary endpoint was not met, no further analyses were completed
Patient reported outcome will also be assessed using SF-36 completed at baseline, Week 12 and Week 24. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Weeks 12 and 24Population: analysis was not done as study primary endpoint was not met- since primary endpoint was not met, no further analyses were completed
CGI-change questionnaire will be completed for global assessment of severity. This questionnaire is categorical and measures outcome from "very much better" being best outcome to "very much worse" being the worst outcome
Outcome measures
Outcome data not reported
Adverse Events
Fluoxetine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Fluoxetine
n=8 participants at risk
Dosing will be
* Week 1-4: 20 mg daily
* Week 5-8: 40 mg daily
* Week 9-12: 60 mg daily
* Week 13-24: 80 mg daily
Fluoxetine
|
|---|---|
|
General disorders
headaches
|
50.0%
4/8 • 7 months
|
|
General disorders
excessive yawning
|
25.0%
2/8 • 7 months
|
|
Psychiatric disorders
anxiety
|
25.0%
2/8 • 7 months
|
|
Gastrointestinal disorders
diarrhea
|
37.5%
3/8 • 7 months
|
|
Respiratory, thoracic and mediastinal disorders
acute bronchitis
|
25.0%
2/8 • 7 months
|
|
General disorders
fatigue
|
25.0%
2/8 • 7 months
|
|
Cardiac disorders
increased palpitations
|
25.0%
2/8 • 7 months
|
|
General disorders
dizziness
|
25.0%
2/8 • 7 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place