Clinical trial NCT00706082: Early, Simple and Reliable Detection of Pulmonary Arterial Hypertension (PAH) in Systemic Sclerosis (SSc)
Official title: A Two-stage Prospective Observational Cohort Study in Scleroderma Patients to Evaluate Screening Tests and the Incidence of Pulmonary Arterial Hypertension and Pulmonary Hypertension
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Systemic Sclerosis
Pulmonary Arterial Hypertension
Pulmonary Hypertension
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2008-06-27
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with scleroderma in USA, Canada, UK, Germany, Switzerland, Austria, The Netherlands, Belgium, Sweden, Slovakia, and Turkey.

Brief summary: A two-stage prospective observational cohort study in scleroderma patients to evaluate screening tests and the incidence of pulmonary arterial hypertension and pulmonary hypertension


Eligibility criteria: Inclusion criteria

* Male or female
* Age ≥ 18 years
* Patients with definite diagnosis of SSc by American College of Rheumatology (ACR) criteria (18); including all patients with any other connective tissue diseases (CTD) who, in parallel, meet the ACR criteria for SSc (18)
* SSc disease duration \> 3 years dated from onset of first non-Raynaud feature
* Diffusing capacity of the lung for carbon monoxide (DLCO) \< 60% of predicted

Exclusion criteria

* PH confirmed by RHC before enrolment, i.e. mean pulmonary arterial pressure (mPAP) \> or = 25 mmHg at rest or \> or = 30 mmHg at exercise, independent of PCWP (11)
* RHC within the 12 months before enrolment
* Use of therapy that is considered definite PAH/PH treatment (19) for any indication, within the 6 weeks before enrolment and/or for a total of more than 6 weeks during the 12 months before enrolment: i.e. endothelin receptor antagonists (ERA; e.g. bosentan, sitaxsentan, ambrisentan), phosphodiesterase type 5 inhibitors (PDE5; e.g. sildenafil, tadalafil, vardenafil), prostanoids (e.g. epoprostenol, treprostinil, iloprost, beraprost), and any experimental PAH/PH drugs. Intermittent use of PDE5 inhibitors for male erectile dysfunction is permitted
* Forced vital capacity (FVC) \< 40%
* Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) \< 40 ml/min/1.73 m2 (20), assessed according to local practice
* Previous evidence or previous diagnosis of clinically relevant left heart disease and other relevant conditions, i.e. at least one of the following:

  * Previous ECHO with estimated left ventricular (LV) ejection fraction \< 50%, previous history of cardiogenic pulmonary edema, increased size of left atrium (\> 50 mm)
  * Known significant diastolic dysfunction associated with clinical heart failure or PCWP \> 15mmHg
  * Known significant coronary disease or significant valvular heart disease
  * Evidence of inadequately treated blood pressure, defined as \> 160/90 mmHg and/or blood pressure during exercise \> 220/120 mmHg (if evaluated)
  * Known hypertrophic cardiomyopathy or left ventricular hypertrophy (interventricular septum thickness (IVS) or posterior wall thickness (PWD) \> 1.2 cm)
  * Patients referred with overt heart failure
  * Known congenital heart defects such as single ventricle, transposition, or Eisenmenger physiology
  * Previous closure of systemic pulmonary shunt, heart valve replacement, or cardiac transplantation
* Pregnancy: pregnancy testing in females with child-bearing potential is mandatory and must be done before enrolment
* Patients unlikely to be available for annual follow up over an anticipated 3 years of study (e.g. survival estimate, psychological, logistics; based on investigator discretion)

Patients with clinically relevant left heart disease as defined above, diagnosed by ECHO at baseline (i.e. after enrolment), will be included in the study.

Additional exclusion criteria after patient enrolment

* During the study, use of therapy that is considered definite PAH/PH treatment (19) is prohibited and will result in discontinuation of the patient from the study, unless the total treatment duration per year is less than 6 weeks. Intermittent use of PDE5 inhibitors for male erectile dysfunction is permitted.
* During the study, use of therapy that is considered definite PAH/PH treatment (19) is prohibited within the 6 weeks preceding the follow-up visits. Violation of this rule will result in discontinuation of the patient from the study.

Primary outcomes:
measure: Pulmonary arterial hypertension (PAH) confirmed by right heart catheterization (RHC)
timeFrame: Baseline and 3-year follow-up
Secondary outcomes:
measure: Pulmonary hypertension (PH) confirmed by right heart catheterization (RHC)
timeFrame: Baseline and 3-year follow-up
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, 311 THT
state: Alabama
city: Los Angeles
country: United States
facility: UCLA Division of Rheumatology
state: California
city: Torrance
country: United States
facility: Harbor UCLA Medical Center
state: California
city: Farmington
country: United States
facility: University of CT
state: Connecticut
city: Washington
country: United States
facility: Department of Rheumatology
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Chicago
country: United States
facility: Rheumatology, MC 733, The University of Illinois-Chicago
state: Illinois
city: Baltimore
country: United States
facility: John Hopkins, Division of Rheumatology
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Scleroderma Program
state: Michigan
city: Grand Rapids
country: United States
facility: Michigan State University
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Division of Rheumatology
state: Minnesota
city: Albany
country: United States
facility: The Center for Rheumatology
state: New York
city: Lake Success
country: United States
facility: Division of Rheumatology and Allergy - Clinical Immunology
state: New York
city: Rochester
country: United States
facility: AAIR Research Center
state: New York
city: Wilmington
country: United States
facility: Carolina Arthritis
state: North Carolina
city: Toledo
country: United States
facility: Chief of Rheumatology
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, Division of Rheumatolgoy and Immunology
state: South Carolina
city: Seattle
country: United States
facility: Department of Critical Care - Virginia Mason Medical Center
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin and Froedtert Hospital
state: Wisconsin
city: Graz
country: Austria
facility: Division of Pulmonology, MEDUK
city: Innsbruck
country: Austria
facility: Universitaetsklinik fuer Dermatologie und Venerologie
city: Linz
country: Austria
facility: Abteilung für Dermatologie
city: Wien
country: Austria
facility: Univ - Klinik fuer Innere Medizin II, Abt. fuer Kardiologie - Medizinische Universitaetsklinik Wien
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinic for Heart and Rheumatic Diseases
city: Belo Horizonte
country: Brazil
facility: Santa Casa de BH - Departamento de Reumatologia
city: Campinas
country: Brazil
facility: Clinical Hospital - UNICAMP University of Campinas
city: Curitiba
country: Brazil
facility: Clinical Hospital - Federal University of Parana State - Rheumatology and Systemic Sclerosis Department
city: Ilha do Fundão
country: Brazil
facility: UFRJ - Serviço de Reumatologia
city: Porto Alegre
country: Brazil
facility: Complexo Santa Casa de POA - Hospital Santa Clara
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS - Pontifícia Universidade Católica de Porto Alegre (PUCRS)
city: São Paulo
country: Brazil
facility: Clinical Hospital - Medicine School of the University of Sao Paulo
city: São Paulo
country: Brazil
facility: Clinical Hospital - Federal University of Medicine of Sao Paulo
city: Calgary
country: Canada
facility: Faculty of Medicine
state: Alberta
city: Edmonton
country: Canada
facility: 2E4.31 Walter Mackenzie Health Sciences Center
state: Alberta
city: Vancouver
country: Canada
facility: Regent Medical Building
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre-VG Site
state: Nova Scotia
city: London
country: Canada
facility: St. Joseph Health Care
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hospital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: Sir Mortimer B Davis Jewish General Hospital
state: Quebec
city: Saskatoon
country: Canada
facility: St. Paul's (Grey Nuns) Hospital
state: Saskatchewan
city: Beijing
country: China
facility: Peking Union Medical College Hospital (West Campus) Chinese Academy of Medical Sciences
city: Praha
country: Czech Republic
facility: Revmatologicky ustav
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik GmbH - Abteilung Rheumatologie und Kliniscihe Immunologie
city: Berlin
country: Germany
facility: Universitaetsmedizine Charite
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonnn
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus
city: Erlangen
country: Germany
facility: Medizinische Klinik 3, Rheumatologie, Immunologie und Onkologie
city: Frankfurt
country: Germany
facility: Goethe-Universitaet Frankfurt
city: Freiburg
country: Germany
facility: Medizinische Klinik der Albert-Ludwigs Universitaet Freiburg
city: Greifswald
country: Germany
facility: Universitatsklinik Greifswald - Klinik fur Innere Medizin B
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitätsklinikum Heidelberg
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Muenster
country: Germany
facility: Medizinische Klinik und Poliklinik B, Rheumatologisch Immunologische Ambulanz
city: Trier
country: Germany
facility: Brüder Krankenhaus
city: Zurich
country: Germany
facility: University Hospital Zurich
city: Debrecen
country: Hungary
facility: Kardiovaszkuláris Ambulancia Kft.
city: Pecs
country: Hungary
city: Nijmegen
country: Netherlands
facility: UMC St Radboud
city: Bergen
country: Norway
facility: Helse Bergen HF Haukeland Universitetssykehus
city: Oslo
country: Norway
facility: Rikshospitalet, University hospital of Oslo - Rheumatology department
city: Trondheim
country: Norway
facility: St. Olav University Hospital - Rheumatologisk avdeling
city: Bialystok
country: Poland
facility: Prywatny Specjalistyczny Gabinet Profesora Stanislawa
city: San Juan
country: Puerto Rico
facility: UPR - Medical Sciences Campus
city: Cluj Napoca
country: Romania
facility: Clinica de Reumatologie
city: Moscow
country: Russian Federation
facility: State Institution "Institute of the Rheumatology of the Russian Academy of Medical Sciences"
city: Piestany
country: Slovakia
facility: The National Institute of Rheumatic Diseases
city: Barcelona
country: Spain
facility: HOSPITAL SANTA CREU i SANT PAU
city: Bizkaia
country: Spain
facility: Servicio de Medicina Interna Planta 2ºB
city: Valencia
country: Spain
facility: Jefe de Servicio - Servicio de Rheumatología
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Adana
country: Turkey
facility: Cukurova Universitesi Tip Fakultesi Balcali Hastanesi
city: Ankara
country: Turkey
facility: Ankara Numune Egitim ve Arastirma hastanesi
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi
city: Izmir
country: Turkey
facility: Ege Universitesi
city: London
country: United Kingdom
facility: Royal Free Hospital NHS Trust
Study officials:
References:
citation: Gopal DM, Doldt B, Finch K, Simms RW, Farber HW, Gokce N. Relation of novel echocardiographic measures to invasive hemodynamic assessment in scleroderma-associated pulmonary arterial hypertension. Arthritis Care Res (Hoboken). 2014 Sep;66(9):1386-94. doi: 10.1002/acr.22307.