Multi-center, Web Based Observational Study of Pulmonary Hypertension in Scleroderma Patients

• ClinicalTrials.gov Identifier: NCT00377949
• Recruitment Status: Completed
• First Posted: September 19, 2006
• Last Update Posted: May 3, 2016
• Sponsor: Georgetown University
• Collaborator: Gilead Sciences
• Information provided by (Responsible Party): Virginia Steen, MD, Georgetown University

Study Description

Brief Summary:

The purpose of this study is to determine the timeline of progression from pre-pulmonary hypertension to diagnosable pulmonary hypertension based on right heart catheterization. Moreover, to determine the timeline for progression from diagnosable pulmonary hypertension to clinical worsening of disease as defined as death, hospitalization, or worsening of PHT symptoms.

Condition or disease
Systemic Sclerosis; Scleroderma; Pulmonary Hypertension; Pulmonary Arterial Hypertension

Detailed Description:

Systemic sclerosis (SSc) is a rare, often fatal idiopathic disease, which has no effective therapy. One of the most major complications of systematic sclerosis is pulmonary hypertension (PHT), which is now the cause of all scleroderma related deaths. New therapeutic advances have improved short-term management of pulmonary hypertension in scleroderma, but long-term outcomes are unknown. With this in mind, Dr. Steen has developed Pulmonary Hypertension Assessment Registry of Scleroderma (PHAROS), a preventive, multi-center, web based observational study that looks at the natural history and outcome of scleroderma patients who are at high risk or have early pulmonary hypertension. Patients entered into the registry will be followed in prospective fashion noting the clinical course of disease by both scheduled and event driven follow up. A thorough baseline history will be collected to determine key prognostic and correlative factors for both disease prevalence and progression. Yearly follow up consisting of questionnaires, pulmonary function tests, echocardiogram, 6 minute walk tests and predefined patient characteristics will also be conducted to further understand and note the progression of scleroderma related PAH. Event driven follow up will occur to record findings and record specific predetermined events in the clinical course of disease.

Study Design

• Study Type: Observational
• Actual Enrollment: 602 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: The Natural History and Outcome of Patients With Scleroderma at High Risk for or With Early Pulmonary Hypertension
• Study Start Date: February 2005
• Actual Primary Completion Date: January 2016

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Pulmonary Hypertension Progression [ Time Frame: 10 years ]
   The primary objective of the study is to determine the timeline of progression from pre-pulmonary hypertension to diagnosable pulmonary hypertension based on right heart catheterization

Biospecimen Retention:   Samples Without DNA

Serum stored for future analysis

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Primary care, rheumatology and pulmonary hypertension clinics.

Criteria

1. Global Inclusion Criteria

   • Eligible patients must meet all of the following inclusion criteria:
   • Patient ≥ 18 years with a clinical diagnosis of SSc (ACR criteria or the LeRoy criteria for limited or diffuse scleroderma

2. Specific Inclusion Criteria

   • Diagnosis of "pre" pulmonary arterial hypertension defined as:
   • Echocardiogram with a resting sPAP of ≥ 40mmHg Or
   • Pulmonary function test with FVC >70% and a DLCO <55% of predicted or a FVC/DLco ratio >1.6. or
   • Right heart catheterization which shows or a mean PA pressure > 30mmHg with exercise (with a mPAP < 25mmHg at rest)

Patients entered as a 'pre'-pulmonary arterial hypertension who then undergo right heart catheterization and are found to have pulmonary arterial hypertension, pulmonary venous hypertension or diastolic dysfunction or pulmonary hypertension secondary to interstitial lung disease will be followed as a definite PH patient and classified into the appropriate category.

• Diagnosis of definite pulmonary hypertension Patients with pulmonary hypertension with a right heart catheterization showing a mean PA pressure > 25mmHg, diagnosed in the past 6 months.

Classification of PH Group 1 PAH - Patients with mPAP ≥ 25mmHg with a wedge < 15mmHg Group 2 PVH - Patients who have a mean PA pressure ≥ 25mmHg with a wedge pressure which is > 15 mmHg Group 3 PH-ILD Patients who have a mean PA pressure ≥ 25mmHg (on right heart catheterization) who have moderate to severe interstitial fibrosis on HRCT scan with a FVC and TLC < 65% predicted

b. Exclusion Criteria

• Diagnosis and treatment of pulmonary hypertension for > 6 months
• Patients with known severe interstitial fibrosis, pulmonary thrombotic disease, heart failure, cardiomyopathy,history of coronary artery disease or other cardio-pulmonary problems which could cause pulmonary hypertension are not eligible for the 'pre'-pulmonary hypertension but do qualify for the definite pulmonary hypertension group if they have a right heart catheterization showing a mean PAH >25mmHg.

Contacts and Locations

Locations

United States, California

UCLA Medical Center

Los Angeles, California, United States, 90095

Stanford University

Stanford, California, United States, 94305

United States, Colorado

National Jewish Medical and Research Center

Denver, Colorado, United States, 80206

United States, District of Columbia

Georgetown University Medical Center

Washington, District of Columbia, United States, 20007

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

University of Chicago

Chicago, Illinois, United States, 60637

United States, Louisiana

Louisiana State University Health Science Center

New Orleans, Louisiana, United States, 70112

United States, Maryland

John Hopkins University Medical Center

Baltimore, Maryland, United States, 21224

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

Boston University Medical School

Boston, Massachusetts, United States, 02118

University of Massachussetts Memorial Medical Center

Worcester, Massachusetts, United States, 01605

United States, Michigan

University of Michigan-Scleroderma Program

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

Hennepin County Medical Center

Minneapolis, Minnesota, United States, 55415

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, New Jersey

University of Medicine and Dentistry of New Jersey

New Brunswick, New Jersey, United States, 08903

United States, New York

Center for Rheumatology

Albany, New York, United States, 12206

North Shore Long Island Jewish Medical Center

New Hyde Park, New York, United States, 11040

Hospital for Special Surgery

New York, New York, United States, 10021

Cornell University

New York, New York, United States, 10065

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15261

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Texas

The University of Texas Health Science Center

Houston, Texas, United States, 77030

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

United States, Wisconsin

The Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Georgetown University

Gilead Sciences

Investigators

• Principal Investigator: Virginia D. Steen, MD; Georgetown University

More Information

Publications:

Young RH, Mark GJ. Pulmonary vascular changes in scleroderma. Am J Med. 1978 Jun;64(6):998-1004. doi: 10.1016/0002-9343(78)90455-2.

Salerni R, Rodnan GP, Leon DF, Shaver JA. Pulmonary hypertension in the CREST syndrome variant of progressive systemic sclerosis (scleroderma). Ann Intern Med. 1977 Apr;86(4):394-9. doi: 10.7326/0003-4819-86-4-394.

Stupi AM, Steen VD, Owens GR, Barnes EL, Rodnan GP, Medsger TA Jr. Pulmonary hypertension in the CREST syndrome variant of systemic sclerosis. Arthritis Rheum. 1986 Apr;29(4):515-24. doi: 10.1002/art.1780290409.

Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH, Koerner SK, Langleben D, Keller CA, Murali S, Uretsky BF, Clayton LM, Jobsis MM, Blackburn SD, Shortino D, Crow JW; Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996 Feb 1;334(5):296-301. doi: 10.1056/NEJM199602013340504.

Steen VD, Ziegler GL, Rodnan GP, Medsger TA Jr. Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis. Arthritis Rheum. 1984 Feb;27(2):125-31. doi: 10.1002/art.1780270202.

Murata I, Takenaka K, Yoshinoya S, Kikuchi K, Kiuchi T, Tanigawa T, Ito K. Clinical evaluation of pulmonary hypertension in systemic sclerosis and related disorders. A Doppler echocardiographic study of 135 Japanese patients. Chest. 1997 Jan;111(1):36-43. doi: 10.1378/chest.111.1.36.

Denton CP, Cailes JB, Phillips GD, Wells AU, Black CM, Bois RM. Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis. Br J Rheumatol. 1997 Feb;36(2):239-43. doi: 10.1093/rheumatology/36.2.239.

MacGregor AJ, Canavan R, Knight C, Denton CP, Davar J, Coghlan J, Black CM. Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival. Rheumatology (Oxford). 2001 Apr;40(4):453-9. doi: 10.1093/rheumatology/40.4.453.

Yousem SA. The pulmonary pathologic manifestations of the CREST syndrome. Hum Pathol. 1990 May;21(5):467-74. doi: 10.1016/0046-8177(90)90002-m.

• Responsible Party: Virginia Steen, MD, Project Principal Investigator, Georgetown University
• ClinicalTrials.gov Identifier: NCT00377949
• Other Study ID Numbers: IRB # 04-227
• First Posted: September 19, 2006
• Last Update Posted: May 3, 2016
• Last Verified: May 2016

Keywords provided by Virginia Steen, MD, Georgetown University:

Systemic Sclerosis; Scleroderma; Pulmonary Hypertension; PHAROS; PHROS; Exercise Echocardiogram; Pulmonary Functional Tests; Six minute walk tests; 6 minute walk tests; Right heart catheterization

Additional relevant MeSH terms:

Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hypertension; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized; Sclerosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases; Connective Tissue Diseases; Skin Diseases