Back to resultsExercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan
Primary Purpose
Systemic Sclerosis, Shortness of Breath, Pulmonary Hypertension
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ambrisentan
Sponsored by
About this trial
This is an interventional treatment trial for Systemic Sclerosis focused on measuring Systemic Sclerosis, connective tissue disease, Shortness of breath, Pulmonary Hypertension
Eligibility Criteria
Inclusion Criteria:
Systemic Sclerosis diagnosed by the American College of Rheumatology consensus statement including any of the following:
- Limited
- Diffuse
- Sine Scleroderma
- Patients must be willing and able to undergo right heart catheterization with lower extremity cycle ergometry
- Mean pulmonary artery pressure (mPAP) > 30mmHg with exercise; PCWP ≤ 15mmHg on RHC at rest
- Men and women, ages 18 years of age or older
- 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:
- Resting PAH (mPAP > 25mmHg) on right heart catheterization
- 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
- Severe hepatic disease precluding the use of ambrisentan (AST/ALT ≥3x ULN).
- Women who are pregnant or breastfeeding.
- Concurrent therapy with a prostanoid or prostanoid analogue, PDE5 inhibitors, or enrolled in another active clinical study.
- Use of any prostacyclin or endothelial receptor antagonist (ERA) within 30 days before study entry.
- Bed or wheel chair bound or a baseline 6-Minute Walk distance (6MWD) less than 150 meters.
- Childbearing capable women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period.
- New York Heart Association (NYHA) Classification: Class IV
- Renal dysfunction (serum creatinine >2.5mg/dL).
- Uncontrolled sleep apnea.
Sites / Locations
- David Geffen School of Medicine, University of California, Los Angeles
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ambrisentan
Arm Description
ambrisentan dosed at either 5mg or 10mg orally once per day
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Change in Distance Walked in Six Minutes From Baseline to 24 Week
ATS guideline based assessment with known minimally clinically important difference
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
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).
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.
Full Information
NCT ID
NCT01051960
First Posted
January 19, 2010
Last Updated
October 28, 2020
Sponsor
University of California, Los Angeles
Collaborators
Gilead Sciences
1. Study Identification
Unique Protocol Identification Number
NCT01051960
Brief Title
Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan
Official Title
Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan: A Prospective Single Center, Open Label, Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
March 2009 (Actual)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Los Angeles
Collaborators
Gilead Sciences
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Sclerosis, Shortness of Breath, Pulmonary Hypertension
Keywords
Systemic Sclerosis, connective tissue disease, Shortness of breath, Pulmonary Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ambrisentan
Arm Type
Experimental
Arm Description
ambrisentan dosed at either 5mg or 10mg orally once per day
Intervention Type
Drug
Intervention Name(s)
Ambrisentan
Other Intervention Name(s)
Letairis
Intervention Description
Ambrisentan 5mg or 10mg once daily
Primary Outcome Measure Information:
Title
Change in Exercise Pulmonary Hemodynamics From Baseline to Week 24
Description
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).
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change in Distance Walked in Six Minutes From Baseline to 24 Week
Description
ATS guideline based assessment with known minimally clinically important difference
Time Frame
24 weeks
Title
Quality of Life (QOL) Based on SF36 and HAQ-DI
Description
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
Time Frame
24 weeks
Title
HAQ-DI (Health Assessment Questionnaire Disability Index)
Description
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).
Time Frame
24 weeks
Title
St. George's Respiratory Questionnaire
Description
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.
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Systemic Sclerosis diagnosed by the American College of Rheumatology consensus statement including any of the following:
Limited
Diffuse
Sine Scleroderma
Patients must be willing and able to undergo right heart catheterization with lower extremity cycle ergometry
Mean pulmonary artery pressure (mPAP) > 30mmHg with exercise; PCWP ≤ 15mmHg on RHC at rest
Men and women, ages 18 years of age or older
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:
Resting PAH (mPAP > 25mmHg) on right heart catheterization
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
Severe hepatic disease precluding the use of ambrisentan (AST/ALT ≥3x ULN).
Women who are pregnant or breastfeeding.
Concurrent therapy with a prostanoid or prostanoid analogue, PDE5 inhibitors, or enrolled in another active clinical study.
Use of any prostacyclin or endothelial receptor antagonist (ERA) within 30 days before study entry.
Bed or wheel chair bound or a baseline 6-Minute Walk distance (6MWD) less than 150 meters.
Childbearing capable women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period.
New York Heart Association (NYHA) Classification: Class IV
Renal dysfunction (serum creatinine >2.5mg/dL).
Uncontrolled sleep apnea.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rajeev Saggar, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dinesh Khanna, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
David Geffen School of Medicine, University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22777623
Citation
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.
Results Reference
result
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Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan
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