Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan

Pulmonary Hypertension Clinical Trial

Official title:

Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan: A Prospective Single Center, Open Label, Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01051960
• Other study ID #: 10-000567
• Status: Completed
• Phase: Phase 4
• Start date: March 2009
• Est. completion date: January 2011

Study information

• Verified date: October 2020
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 2011
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dyspnea
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Shortness of Breath
• Systemic Sclerosis

Intervention

Drug:
• Ambrisentan
Ambrisentan 5mg or 10mg once daily

Locations

Country	Name	City	State
United States	David Geffen School of Medicine, University of California, Los Angeles	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Exercise Pulmonary Hemodynamics From Baseline to Week 24	We defined ePH (exercise PH) as an mPAP of 30 mmHg, PCWP of 18 mm Hg, and a transpulmonary gradient (TPG) of 15 mm Hg, where TPG equals mPAP minus PCWP. We defined ePVH (exercise pulmonary venous hypertension) as an mPAP of 30 mm Hg, PCWP of 18 mm Hg, and a TPG of 15 mm Hg. We defined eoPH (exercise out of proportion) as an mPAP of 30 mm Hg, PCWP of 18 mm Hg, and a TPG of 15 mm Hg (4). Our hypothesis was that SSc patients with normal exercise physiology and ePVH have a different patho-physiology compared to patients with pulmonary vascular disease (ePH and eoPH).	24 weeks
Secondary	Change in Distance Walked in Six Minutes From Baseline to 24 Week	ATS guideline based assessment with known minimally clinically important difference	24 weeks
Secondary	Quality of Life (QOL) Based on SF36 and HAQ-DI	Number of participants exceeding minimally important difference estimates on changes in quality of life as assessed by SF-36 (short form 36) quality of life index with mental and physical component scores, or by HAQ-DI (health assessment questionnaire disability index) limitations that may be related to musculoskeletal limitations	24 weeks
Secondary	HAQ-DI (Health Assessment Questionnaire Disability Index)	Assessing limitations that may be related to musculoskeletal limitations, the HAQ-DI assesses the difficulty a participant has had in the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items in which level of difficulty is scored from 0 to 3 with 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. The 8 domain scores are averaged into a total HAQ-DI score ranging from 0 (no disability) to 3 (completely disabled).	24 weeks
Secondary	St. George's Respiratory Questionnaire	To assess overall health, daily life, and perceived well-being in patients with underlying lung disease, the SGRQ is a health-related quality of life questionnaire divided into 3 components : symptoms, activity and impact. The total score (summed weights) can range from 0 to 100 with a lower score denoting a better health status.	24 weeks