The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: Ambrisentan plus Spironolactone; Ambrisentan plus Placebo
Intervention description: Cardiopulmonary fitness; Placebo is a sugar pill manufactured to resemble spironolactone 50 mg Cardiopulmonary fitness
Intervention MeSH terms: Ambrisentan; Spironolactone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pulmonary Arterial Hypertension (PAH); Ambrisentan; Spironolactone; Selective Endothelin A (ETA) inhibition; Aldosterone antagonism; Cardiac output (CO); Right ventricular (RV) function; Heart failure; Quality of life; Pro-inflammatory cytokine; Interleukin-6 (IL-6); Troponin-I; N-terminal pro-brain natriuretic peptide (NT-BNP); Collagen metabolism; N-terminal procollagen type I; Collagen III; Echocardiography; WHO Functional Class; Cardiopulmonary Exercise Test with Innocor; Peak oxygen consumption (pVO2); Liver function markers (AST/ALT); Renal function markers (creatinine and potassium)

Summary:

      The purpose of this study is to find out if spironolactone added to ambrisentan for Pulmonary
      Arterial Hypertension (PAH) will increase exercise capacity. We also want to find out if
      spironolactone and ambrisentan effect the cardiac output (amount of blood the heart pumps
      every minute), right ventricle function and quality of life.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Voluntarily gives informed consent to participate in the study.

          2. Right heart catheterization demonstrating conventional mean pulmonary artery pressure
             (mPAP) >25, pulmonary vascular resistance (PVR) >3.0 Wood Units, pulmonary capillary
             wedge pressure (PCWP) <16 mmHg within two years of enrollment

          3. Subject is 18 years of age or older at Screening.

          4. Diagnosis of symptomatic idiopathic or heritable PAH, PAH associated with Connective
             Tissue Disease (CTD), PAH associated with repaired/unrepaired congenital
             systemic-to-pulmonary shunt, Portopulmonary hypertension or PAH associated with HIV
             infection.

          5. New York Heart Association Functional Class II or III

          6. Stable therapy with ambrisentan 5 or 10 mg every day for > 90 days.

          7. Baseline 6-Minute Walk Distance 50-450m

        Exclusion Criteria:

          1. Substantial Primary Lung disease

               -  forced expiratory volume at one second (FEV-1)/forced vital capacity (FVC) <0.6
                  and FEV-1 <70% predicted

               -  diffusing capacity of lung for carbon monoxide (DLCO) <30% predicted

               -  Pulmonary fibrosis

          2. Left ventricular ejection fraction < 50%

          3. Pulmonary capillary wedge pressure > 16 mm Hg

          4. Aortic valve disease

          5. Ischemic heart disease

          6. Systemic hypotension (SBP <90 mm Hg)

          7. Co-existing treatment with other endothelin receptor antagonists or prostacyclin
             analogues

          8. New York Heart Association Functional Class IV

          9. Chronic thromboembolic pulmonary hypertension

         10. Known or suspected pulmonary veno-occlusive disease

         11. Serum creatinine >2.0 mg/dL in women, Serum creatinine >2.5 mg/dL in men

         12. Baseline serum potassium >5.0 milliequivalent (mEq)/L

         13. Participation in ongoing drug/intervention-based clinical trial

         14. Pregnancy

         15. Unable to provide consent