Clinical trial NCT00377949: Multi-center, Web Based Observational Study of Pulmonary Hypertension in Scleroderma Patients
Official title: The Natural History and Outcome of Patients With Scleroderma at High Risk for or With Early Pulmonary Hypertension
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Sclerosis
Scleroderma
Pulmonary Hypertension
Pulmonary Arterial Hypertension
Keywords: Systemic Sclerosis
Scleroderma
Pulmonary Hypertension
PHAROS
PHROS
Exercise Echocardiogram
Pulmonary Functional Tests
Six minute walk tests
6 minute walk tests
Right heart catheterization
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2006-09-19
Enrollment: 602
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Primary care, rheumatology and pulmonary hypertension clinics.

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.

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.

Eligibility 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.

Primary outcomes:
measure: Pulmonary Hypertension Progression
timeFrame: 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: New Orleans
country: United States
facility: Louisiana State University Health Science Center
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins University Medical Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical School
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachussetts Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan-Scleroderma Program
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New Brunswick
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Albany
country: United States
facility: Center for Rheumatology
state: New York
city: New Hyde Park
country: United States
facility: North Shore Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Cornell University
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: The University of Texas Health Science Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Georgetown University
name: Virginia D. Steen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.7326/0003-4819-86-4-394.
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. doi: 10.1002/art.1780290409.
citation: 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.
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. doi: 10.1002/art.1780270202.
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. doi: 10.1378/chest.111.1.36.
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. doi: 10.1093/rheumatology/36.2.239.
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. doi: 10.1093/rheumatology/40.4.453.
citation: 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.