Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan - Full Text View

Sponsor:	University of California, Los Angeles
Collaborator:	Gilead Sciences
Information provided by:	University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT01051960

Purpose

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	Intervention	Phase
Systemic Sclerosis Shortness of Breath Pulmonary Hypertension	Drug: Ambrisentan	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: systemic scleroderma

MedlinePlus related topics: Breathing Problems Exercise and Physical Fitness High Blood Pressure Pulmonary Hypertension Scleroderma

Drug Information available for: Ambrisentan

U.S. FDA Resources

Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:

Change in multipoint exercise total pulmonary resistance (TPR)from baseline to week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	15
Study Start Date:	March 2009
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Ambrisentan 5mg or 10mg once daily

Other Name: Letairis

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01051960

Contacts

Contact: Rajeev Saggar, MD	310-825-5635	rasaggar@mednet.ucla.edu
Contact: Amber Betchel	310-825-0425	ABechtel@mednet.ucla.edu

Locations

United States, California
David Geffen School of Medicine, University of California, Los Angeles	Recruiting
Los Angeles, California, United States, 90095
Contact: Amber Betchel 310-825-0425 abetchel@mednet.ucla.edu
Contact: Rajeev Saggar, MD 310-825-5635 rasaggar@mednet.ucla.edu
Sub-Investigator: Daniel Furst, MD
Sub-Investigator: Shelley Shapiro, MD
Sub-Investigator: Rajan Saggar, MD
Sub-Investigator: Philip Clements, MD

Sponsors and Collaborators

University of California, Los Angeles

Gilead Sciences

Investigators

Principal Investigator:	Rajeev Saggar, MD	University of California, Los Angeles
Principal Investigator:	Dinesh Khanna, MD	University of California, Los Angeles

More Information

No publications provided

Responsible Party:	Rajeev Saggar, MD, David Geffen School of Medicine, University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT01051960 History of Changes
Other Study ID Numbers:	08-05-003
Study First Received:	January 19, 2010
Last Updated:	January 19, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:

Systemic Sclerosis
connective tissue disease
Shortness of breath
Pulmonary Hypertension

Additional relevant MeSH terms:

Dyspnea
Hypertension
Hypertension, Pulmonary
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Respiration Disorders
Respiratory Tract Diseases

Signs and Symptoms, Respiratory
Signs and Symptoms
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Connective Tissue Diseases
Skin Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on February 09, 2012