Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by University of California, Los Angeles.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Gilead Sciences
Information provided by:
University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01051960
First received: January 19, 2010
Last updated: NA
Last verified: February 2009
History: No changes posted

January 19, 2010
January 19, 2010
March 2009
June 2010   (final data collection date for primary outcome measure)
Change in multipoint exercise total pulmonary resistance (TPR)from baseline to week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Same as current
No Changes Posted
  • Change in distance walked in six minutes from baseline to 24 week [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • SF-36, HAQ-DI, and St. George's respiratory questionnaire total score from baseline to 24 weeks of therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan
Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan: A Prospective Single Center, Open Label, Pilot Study

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

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.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Systemic Sclerosis
  • Shortness of Breath
  • Pulmonary Hypertension
Drug: Ambrisentan
Ambrisentan 5mg or 10mg once daily
Other Name: Letairis
Not Provided
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
15
December 2010
June 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact: Rajeev Saggar, MD 310-825-5635 rasaggar@mednet.ucla.edu
Contact: Amber Betchel 310-825-0425 ABechtel@mednet.ucla.edu
United States
 
NCT01051960
08-05-003
No
Rajeev Saggar, MD, David Geffen School of Medicine, University of California, Los Angeles
University of California, Los Angeles
Gilead Sciences
Principal Investigator: Rajeev Saggar, MD University of California, Los Angeles
Principal Investigator: Dinesh Khanna, MD University of California, Los Angeles
University of California, Los Angeles
February 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP