Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan

NCT ID: NCT01051960

Last Updated: 2020-11-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2011-01-31

Brief 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

Detailed 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.

Conditions

Systemic Sclerosis; Shortness of Breath; Pulmonary Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ambrisentan

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

Group Type: EXPERIMENTAL

Ambrisentan

Intervention Type: DRUG

Ambrisentan 5mg or 10mg once daily

Interventions

Ambrisentan

Ambrisentan 5mg or 10mg once daily

Intervention Type: DRUG

Other Intervention Names

Letairis

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rajeev Saggar, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Dinesh Khanna, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

David Geffen School of Medicine, University of California, Los Angeles

Los Angeles, California, United States

Countries

United States

References

Saggar R, Khanna D, Shapiro S, Furst DE, Maranian P, Clements P, Abtin F, Dua S, Belperio J, Saggar R. Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study. Arthritis Rheum. 2012 Dec;64(12):4072-7. doi: 10.1002/art.34614.

Reference Type: RESULT

PMID: 22777623 (View on PubMed)

Other Identifiers

10-000567

Identifier Type: -

Identifier Source: org_study_id