Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

Official title:

Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00942708
• Other study ID #: STU 052009-009
• Secondary ID: UL1RR024982
• Status: Completed
• Phase: Phase 2
• Start date: September 2009
• Est. completion date: August 2011

Study information

• Verified date: May 2020
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety, tolerability and efficacy of open-label fluoxetine for three months among patients with pulmonary arterial hypertension.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: August 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Fluoxetine
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

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Change in PVR at 3 mos (Baseline - 3 months)
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.	Baseline - 3 months (median change)
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.	3 months