Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, Pulmonary Hypertension
Brief summary
This study will evaluate the safety, tolerability and efficacy of open-label fluoxetine for three months among patients with pulmonary arterial hypertension.
Detailed description
Idiopathic pulmonary arterial hypertension (PAH) is a life-threatening disorder of uncertain cause that leads to progressive right heart failure and death. Average survival has improved from about 2.8 years in the early 1990s to approximately 5-7 years with current treatments, but most patients will still die of their disease. Two classes of oral medications are approved for use in PAH: endothelin-1 antagonists, and phosphodiesterase-5 inhibitors. Both improve walk distance and symptoms in PAH, but most patients still have continued dyspnea, fatigue and significant elevations in pulmonary pressures. Those who remain severely impaired are generally started on a continuous intravenous prostacyclin. For those who are less ill but still symptomatic, few options are available. Primary endpoint: the primary endpoint will be change in pulmonary vascular resistance (PVR) measured by right heart catheterization after three months of therapy. Secondary endpoints * Six minute walk distance * QIDS-SR depression scale Safety and tolerability endpoints will include a tabulation of adverse events to include but not limited to: * Death * Hospitalization * Symptomatic hypotension * Gastrointestinal side effects * Depression
Interventions
DRUGFluoxetine
Total dose How to take: Week 1-2 20 mg daily Week 3-4 40 mg daily Week 5-6 40 mg BID Week 7-12 40mg BID
Sponsors
National Center for Research Resources (NCRR)
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent prior to any study-mandated procedure 2. PAH of the following subtypes: idiopathic PAH WHO functional class II-III 3. Catheterization within one week showing mPAP \>=25, wedge or LV end diastolic pressure ≤15, and PVR \> 4 wood units, and baseline fick cardiac output results available 4. Age 16-75 5. Able to complete a six minute walk distance 6. Women of childbearing potential\*: negative serum pre-treatment pregnancy test + consistently and correctly uses a reliable method of contraception\*\* Oral approved PAH therapy for \>3 months with no change in dose for \> 1 month
Exclusion criteria
1. PAH with connective tissue disease, congenital heart disease, portal hypertension, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathy, myeloproliferative disorders. 2. Moderate to severe obstructive or restrictive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) \< 70% and FEV1 \< 60% of predicted value after bronchodilator administration. -or- total lung capacity (TLC) \< 60% of predicted. 3. Systemic systolic blood pressure \<100 mmHg Breastfeeding 4. Significant liver, renal or other medical disease preventing completion of the study procedures or with life expectancy \<12 months, or any other acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pulmonary Vascular Resistance (PVR) at Three Months | Change in PVR at 3 mos (Baseline - 3 months) | PVR will be measured by right heart catheterization at baseline and 3 months. Change in PVR will be determined by baseline value minus 3 month value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change Between Baseline and Three Month in the QIDS-SR Depression Scale | Baseline - 3 months (median change) | The Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR) depression scale is a questionnaire completed by the patient. Lower scores are better. Scoring can be interpreted as 7 or less: normal, 8-12: mild depression, 13-16 moderate depression, 17-20 moderate to severe depression and \>20 severe depression. Results here show the median change between baseline and 3 months, making a positive change in score indicative of improvement. Total minimum score is 0 and the maximum is 27. |
| Change in Six Minute Walk Distance at 3 Months | 3 months | Six minute walk distance will be measured at baseline and after 3 months of fluoxetine. Change in walk distance (mean and SD) will be reported by taking subtracting baseline values from result at 3 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluoxetine Fluoxetine will be added starting at 20 mg and titrated as tolerated to 80 mg daily.
Fluoxetine: :
Week 1-2 20 mg daily Week 3-4 40 mg daily Week 5-12 40 mg BID | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Fluoxetine |
|---|---|
| Age, Continuous | 48.2 years STANDARD_DEVIATION 11.2 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Change in Pulmonary Vascular Resistance (PVR) at Three Months
PVR will be measured by right heart catheterization at baseline and 3 months. Change in PVR will be determined by baseline value minus 3 month value.
Time frame: Change in PVR at 3 mos (Baseline - 3 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine | Change in Pulmonary Vascular Resistance (PVR) at Three Months | -0.49 Wood units | Standard Deviation 0.49 |
p-value: 0.09t-test, 1 sided
Secondary
Change Between Baseline and Three Month in the QIDS-SR Depression Scale
The Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR) depression scale is a questionnaire completed by the patient. Lower scores are better. Scoring can be interpreted as 7 or less: normal, 8-12: mild depression, 13-16 moderate depression, 17-20 moderate to severe depression and \>20 severe depression. Results here show the median change between baseline and 3 months, making a positive change in score indicative of improvement. Total minimum score is 0 and the maximum is 27.
Time frame: Baseline - 3 months (median change)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluoxetine | Change Between Baseline and Three Month in the QIDS-SR Depression Scale | 1 units on a scale |
Secondary
Change in Six Minute Walk Distance at 3 Months
Six minute walk distance will be measured at baseline and after 3 months of fluoxetine. Change in walk distance (mean and SD) will be reported by taking subtracting baseline values from result at 3 months.
Time frame: 3 months
Population: All patients completing the 12 week study were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine | Change in Six Minute Walk Distance at 3 Months | 10 meters | Standard Deviation 48 |