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Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01051960
Recruitment Status : Completed
First Posted : January 20, 2010
Results First Posted : November 2, 2020
Last Update Posted : November 2, 2020
Gilead Sciences
Information provided by (Responsible Party):
University of California, Los Angeles

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

Condition or disease Intervention/treatment Phase
Systemic Sclerosis Shortness of Breath Pulmonary Hypertension Drug: Ambrisentan Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan: A Prospective Single Center, Open Label, Pilot Study
Actual Study Start Date : March 2009
Actual Primary Completion Date : June 2010
Actual Study Completion Date : January 2011

Arm Intervention/treatment
Experimental: ambrisentan
ambrisentan dosed at either 5mg or 10mg orally once per day
Drug: Ambrisentan
Ambrisentan 5mg or 10mg once daily
Other Name: Letairis

Primary Outcome Measures :
  1. Change in Exercise Pulmonary Hemodynamics From Baseline to Week 24 [ Time Frame: 24 weeks ]
    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 :
  1. Change in Distance Walked in Six Minutes From Baseline to 24 Week [ Time Frame: 24 weeks ]
    ATS guideline based assessment with known minimally clinically important difference

  2. Quality of Life (QOL) Based on SF36 and HAQ-DI [ Time Frame: 24 weeks ]
    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

  3. HAQ-DI (Health Assessment Questionnaire Disability Index) [ Time Frame: 24 weeks ]
    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).

  4. St. George's Respiratory Questionnaire [ Time Frame: 24 weeks ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01051960

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United States, California
David Geffen School of Medicine, University of California, Los Angeles
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Gilead Sciences
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Principal Investigator: Rajeev Saggar, MD University of California, Los Angeles
Principal Investigator: Dinesh Khanna, MD University of California, Los Angeles
Publications of Results:
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Responsible Party: University of California, Los Angeles Identifier: NCT01051960    
Other Study ID Numbers: 10-000567
First Posted: January 20, 2010    Key Record Dates
Results First Posted: November 2, 2020
Last Update Posted: November 2, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of California, Los Angeles:
Systemic Sclerosis
connective tissue disease
Shortness of breath
Pulmonary Hypertension
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Scleroderma, Systemic
Scleroderma, Diffuse
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Connective Tissue Diseases
Skin Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Antihypertensive Agents