Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: Fluoxetine
Intervention MeSH terms: Fluoxetine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 16 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This protocol describes an open-label phase 2 clinical trial of fluoxetine in PAH looking at
      change in pulmonary vascular resistance (PVR) as the primary endpoint.

      In this open-label clinical trial, 18 patients with pulmonary arterial hypertension will be
      given fluoxetine for 24 weeks. A Right Heart Catheterization will be performed at baseline
      and 24 weeks. Change in PVR will be the primary endpoint; other hemodynamic endpoints,
      quality of life, QIDS-SR depression scale, functional class and six-minute walk distance will
      also be evaluated.

      Primary Hypothesis: Fluoxetine treatment for 24 weeks will lead to significantly lower
      pulmonary vascular resistance in 18 patients with PAH in patients treated in an open-label
      clinical trial.
    

Eligibility criteria:

        Inclusion Criteria:

          1. WHO Group I PAH subtypes of idiopathic PAH and PAH associated with drugs / toxins,
             connective tissue disease, repaired congenital heart disease and unrepaired atrial
             septal defect

          2. Age 16-80

          3. WHO Functional Class II or III

          4. Right Heart Catheterization within 3 weeks of study entry with mPAP ≥ 25 mmHg, wedge ≤
             15 mmHg, and PVR ≥ 3 Wood units.

          5. Contraception use, (-) urine pregnancy test, not breast feeding (women of childbearing
             potential)

          6. One or more approved PAH therapies for ≥ 3 months, no change in dose for 1 month
             (endothelin-1 antagonist, phosphodiesterase-5 inhibitor, prostacyclin / prostacyclin
             analog). Novel approved therapies in one of the three existing classes will also be
             acceptable as background therapy if they become available during the course of the
             study; other medication classes are excluded

             Exclusion Criteria:

          7. WHO Functional Class IV or listed for lung transplant

          8. Moderate or greater obstructive lung disease: FEV1/FVC <70% and FEV1 <60%

          9. Moderate or greater restrictive lung disease: TLC or FVC <60% (if 50-60%: OK if TLC or
             FVC ≥50% + PFT stable x1 year + CT with no more than mild lung disease)

         10. Other cause for pulmonary hypertension: all other WHO group I diseases (including but
             not limited to liver disease, HIV), and WHO Groups II-V (i.e. left heart disease, lung
             disease, chronic PE and miscellaneous causes)24.

               1. High probability VQ or positive CTA

               2. Left ventricular ejection fraction <40%

         11. Depression

         12. Severe liver, renal or other medical or physical disease preventing completion of the
             study procedures

         13. Use of antidepressants within 3 months