Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan

University of California, Los Angeles (UCLA)

Status and phase: Completed; Phase 4

Conditions: Shortness of Breath; Systemic Sclerosis; Pulmonary Hypertension

Treatments: Drug: Ambrisentan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01051960

10-000567

Details and patient eligibility

About

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

Full description

The current literature addresses therapies for patients with resting PAH only, diagnosed by right heart catheterization. However, the World Health Organization (WHO) also recognizes and defines exercise induced pulmonary arterial hypertension (ex-PAH), which may precede the development of resting PAH. The natural progression of PAH, especially during exercise, has not been well delineated. An exercise hemodynamic study previously showed that in normal healthy subjects the mean pulmonary pressure does not exceed 30mmHg even at maximal cardiac outputs. A prior study evaluated exercise Doppler echocardiography systemic sclerosis patients with normal resting echocardiograms, finding an abnormal response which was defined as an estimated right ventricular systolic pressure greater than 40 mmHg. In the same study, 6.6% of the patients progressed to resting PAH over the followup period of 12 months. Limited data is available regarding the prevalence of ex-PAH in systemic sclerosis using right heart catheterization.

Enrollment: 12 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

ambrisentan

Experimental group

Description:

ambrisentan dosed at either 5mg or 10mg orally once per day

Treatment:

Drug: Ambrisentan