Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension

Official Title: “Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension”

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

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

Efficacy: - Other three month catheterization variables: right atrial pressure, pulmonary arterial pressure, Fick cardiac output, pulmonary arterial oxygen saturation, pulmonary capillary wedge pressure - Six minute walk distance - WHO functional class - Brain natriuretic peptide

Safety and tolerability endpoints will include change between baseline and three month QIDS-SR depression scale, systolic and diastolic blood pressure (systemic) and tabulation of adverse events to include but not limited to: - Death - Hospitalization - Symptomatic hypotension - Gastrointestinal side effects - Depression

Intervention(s) in this Clinical Trial

• 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

Arms, Groups and Cohorts in this Clinical Trial

• Other: Fluoxetine
  • Fluoxetine will be added starting at 20 mg and titrated as tolerated to 80 mg daily.

Primary Measures

• The primary endpoint will be change in pulmonary vascular resistance (PVR) measured by right heart catheterization after three months of therapy.
  • Time Frame: 3 months
    Safety Issue?: Yes

Secondary Measures

• Efficacy, Safety and tolerability endpoints will include change between baseline and three month QIDS-SR depression scale, systolic and diastolic blood pressure (systemic) and tabulation of adverse events
  • Time Frame: 3 months
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of Texas Southwestern Medical Center Other

Overall Clinical Trial Officials and Contacts

Kelly M Chin, MD Principal Investigator UT Southwestern Medical Center  

Overall Contact: Kelly M Chin, MD 214-645-6486 kelly.chin@utsouthwestern.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00942708

Study ID Number: CTSA NIH Grant UL1-RR024982

ClinicalTrials.gov Identifier: NCT00942708

Health Authority: United States: Institutional Review Board