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

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

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.

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis; Pulmonary Arterial Hypertension; Pulmonary Hypertension; Scleroderma

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 Type: Observational
• Enrollment (Actual): 602

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • John Hopkins University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical School
    • Worcester, Massachusetts, United States, 01605
      • University of Massachussetts Memorial Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan-Scleroderma Program
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • University of Medicine and Dentistry of New Jersey
  • New York
    • Albany, New York, United States, 12206
      • Center for Rheumatology
    • New Hyde Park, New York, United States, 11040
      • North Shore Long Island Jewish Medical Center
    • New York, New York, United States, 10065
      • Cornell University
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Primary care, rheumatology and pulmonary hypertension clinics.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Virginia D. Steen, MD, Georgetown University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: September 18, 2006
• First Submitted That Met QC Criteria: September 18, 2006
• First Posted (Estimate): September 19, 2006

Study Record Updates

• Last Update Posted (Estimate): May 3, 2016
• Last Update Submitted That Met QC Criteria: May 2, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Systemic Sclerosis; Scleroderma; Right heart catheterization; PHAROS; PHROS; Exercise Echocardiogram; Pulmonary Functional Tests; Six minute walk tests; 6 minute walk tests
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Respiratory Tract Diseases; Lung Diseases; Connective Tissue Diseases; Sclerosis; Hypertension; Scleroderma, Systemic; Scleroderma, Diffuse; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Scleroderma, Localized
• Other Study ID Numbers: IRB # 04-227