Early, Simple and Reliable Detection of Pulmonary Arterial Hypertension (PAH) in Systemic Sclerosis (SSc)

Pulmonary Hypertension Clinical Trial

— DETECT  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00706082
• Other study ID #: AC-052-510
• Status: Terminated
• Phase: N/A
• First received: June 25, 2008
• Last updated: June 21, 2012
• Start date: October 2008
• Est. completion date: March 2012

Study information

• Verified date: June 2012
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardCanada: Ethics Review CommitteeUnited Kingdom: Research Ethics CommitteeGermany: Ethics CommissionSwitzerland: EthikkommissionAustria: EthikkommissionNetherlands: Independent Ethics CommitteeBelgium: Institutional Review BoardSweden: Institutional Review BoardTurkey: Ethics Committee
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 490
• Est. completion date: March 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Austria,  Bosnia and Herzegovina,  Brazil,  Canada,  China,  Czech Republic,  Germany,  Hungary,  Netherlands,  Norway,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Slovakia,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary arterial hypertension (PAH) confirmed by right heart catheterization (RHC)		Baseline and 3-year follow-up	No
Secondary	Pulmonary hypertension (PH) confirmed by right heart catheterization (RHC)		Baseline and 3-year follow-up	No