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

Pulmonary Hypertension Clinical Trial

Official title:

The Natural History and Outcome of Patients With Scleroderma at High Risk for or With Early Pulmonary Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00377949
• Other study ID #: IRB # 04-227
• Status: Completed
• Phase: N/A
• First received: September 18, 2006
• Last updated: May 2, 2016
• Start date: February 2005

Study information

• Verified date: May 2016
• Source: Georgetown University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 602
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension
• Pulmonary Hypertension
• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Localized
• Scleroderma, Systemic
• Systemic Sclerosis

Locations

Country	Name	City	State
United States	Center for Rheumatology	Albany	New York
United States	University of Michigan-Scleroderma Program	Ann Arbor	Michigan
United States	John Hopkins University Medical Center	Baltimore	Maryland
United States	Boston University Medical School	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	The University of Texas Health Science Center	Houston	Texas
United States	UCLA Medical Center	Los Angeles	California
United States	The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of Medicine and Dentistry of New Jersey	New Brunswick	New Jersey
United States	North Shore Long Island Jewish Medical Center	New Hyde Park	New York
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	Cornell University	New York	New York
United States	Hospital for Special Surgery	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Utah	Salt Lake City	Utah
United States	Stanford University	Stanford	California
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	University of Massachussetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Georgetown University	Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (9)

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, Jöbsis 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Young RH, Mark GJ. Pulmonary vascular changes in scleroderma. Am J Med. 1978 Jun;64(6):998-1004. — View Citation

Yousem SA. The pulmonary pathologic manifestations of the CREST syndrome. Hum Pathol. 1990 May;21(5):467-74. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary Hypertension Progression	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	10 years	No