Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan
Condition: Systemic Sclerosis; Shortness of Breath; Pulmonary Hypertension
MeSH terms: Hypertension, Pulmonary; Dyspnea; Hypertension; Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis
Intervention: Ambrisentan
Intervention description: Ambrisentan 5mg or 10mg once daily
Intervention MeSH terms: Ambrisentan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Systemic Sclerosis; connective tissue disease; Shortness of breath; Pulmonary Hypertension

Summary:

      The purpose of this study is to determine the clinical characteristics and hemodynamic
      profiles that predict exercise induced pulmonary hypertension in 15 patients with systemic
      sclerosis. The study also aims to determine the effectiveness of Ambrisentan for subjects
      with exercise induced Pulmonary Arterial Hypertension (PAH) with scleroderma
    

Eligibility criteria:

        Inclusion Criteria:

          1. Systemic Sclerosis diagnosed by the American College of Rheumatology consensus
             statement including any of the following:

               -  Limited

               -  Diffuse

               -  Sine Scleroderma

          2. Patients must be willing and able to undergo right heart catheterization with lower
             extremity cycle ergometry

          3. Mean pulmonary artery pressure (mPAP) > 30mmHg with exercise; PCWP ≤ 15mmHg on RHC at
             rest

          4. Men and women, ages 18 years of age or older

          5. Standard adjunctive medications will be allowed concurrently in this study at the
             discretion of the treating pulmonologist and rheumatologist, including digoxin,
             diuretics, anticoagulants (e.g. warfarin), stable immunosuppression or other
             anti-fibrotic therapy for at least one month prior to enrollment

        Exclusion Criteria:

          1. Resting PAH (mPAP > 25mmHg) on right heart catheterization

          2. Other known causes of PAH including prior venous thromboembolism, HIV infection,
             chronic liver disease with portal hypertension, left ventricular systolic dysfunction
             (e.g. LVEF < 40%), and congenital causes of PAH

          3. Severe hepatic disease precluding the use of ambrisentan (AST/ALT ≥3x ULN).

          4. Women who are pregnant or breastfeeding.

          5. Concurrent therapy with a prostanoid or prostanoid analogue, PDE5 inhibitors, or
             enrolled in another active clinical study.

          6. Use of any prostacyclin or endothelial receptor antagonist (ERA) within 30 days before
             study entry.

          7. Bed or wheel chair bound or a baseline 6-Minute Walk distance (6MWD) less than 150
             meters.

          8. Childbearing capable women who are unwilling or unable to use an acceptable method to
             avoid pregnancy for the entire study period.

          9. New York Heart Association (NYHA) Classification: Class IV

         10. Renal dysfunction (serum creatinine >2.5mg/dL).

         11. Uncontrolled sleep apnea.