Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial

The University of Texas System (UT)

Status and phase: Completed; Phase 2

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Fluoxetine

Study type: Interventional

Funder types: Other

Identifiers

NCT03638908

NIKK23

STU 082013-045 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 16 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Fluoxetine

Other group

Description:

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

Treatment:

Drug: Fluoxetine