Study of the Efficacy and Safety of Tezosentan in Patients With Pre-operative Pulmonary Hypertension, Due to Left Heart Disease, Undergoing Open Heart Surgery
Information source: Actelion
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Heart Diseases; Hypertension, Pulmonary
Intervention: tezosentan (Drug); placebo (Drug)
Phase: Phase 3
Status: Terminated
Sponsored by: Actelion Official(s) and/or principal investigator(s): Andre Denault, Prof., Study Chair, Affiliation: Montreal Heart Institute Ronald Pearl, MD, Study Chair, Affiliation: Stanford University Robert Michler, MD, Study Chair, Affiliation: Montefiore Medical Center Steven Tsui, Study Chair, Affiliation: Papworth Hospital Rainald Seitelberger, Prof., Study Chair, Affiliation: AKH University of Vienna Andrea D'Armini, Prof., Study Chair, Affiliation: San Matteo Hospital
Summary
Endothelin-1 is a powerful substance that may be involved in causing hemodynamic instability
(problems related to unstable blood pressure) during and after open heart surgery.
Tezosentan is an investigational intravenous drug that blocks the endothelin receptors.
This clinical trial will assess the potential benefit of tezosentan compared with placebo in
the treatment of patients undergoing open heart surgery with cardiopulmonary bypass (CPB).
Treatment time is from the start of surgery up to 24 hours.
Clinical Details
Official title: Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of Tezosentan in Patients With Pre-operative Pulmonary Hypertension, Due to Left Heart Disease, Undergoing Cardiac Surgery
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: The primary objective of this trial is to demonstrate that tezosentan, a dual ERA, reduces the incidence of clinically relevant right ventricular failure in patients with pre-operative pulmonary hypertension, due to left heart disease, undergoing CPB.
Secondary outcome: Proportion of patients w/a major clinical event w/in 28 days after study drug initiation like death/major cardiovascular events/infections that prolong hospital stay or require re-admission/new onset of renal failure requiring renal replacement therapyTime to weaning from cardiopulmonary bypass Time from end of CPB to final discharge from Intensive Care Unit (ICU)
Detailed description:
Endothelin-1 levels are increased during and after cardiac surgery with cardiopulmonary
bypass (CPB), and are associated with many deleterious consequences, including increased
pulmonary arterial pressure (PAP), increased pulmonary vascular resistance (PVR), reduced
myocardial contractility, and ultimately right ventricular failure. Right ventricular
failure during weaning from CPB increases the risk of mortality and morbidity, especially in
patients with elevated PAP prior to cardiac surgery. Endothelin receptor antagonists (ERAs)
have been shown to decrease PVR and pulmonary arterial pressure (PAP), and improve right
ventricular function in patients with pulmonary arterial hypertension. In animal models,
ERAs have been shown to decrease the incidence of post-bypass pulmonary hypertensive crises.
The primary objective of this trial is to demonstrate that tezosentan, a dual ERA, reduces
the incidence of clinically relevant right ventricular failure in patients with
pre-operative pulmonary hypertension, due to left heart disease, undergoing CPB.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients ≥ 18 years of age
- Male or female patients (females of child-bearing potential must have been surgically
sterilized or use a reliable method of contraception).
- Patients undergoing complex* cardiac surgery on CPB and having systolic PAP > 40 mmHg
or mean PAP > 30 mmHg (*surgery on 2 valves, 1 valve and revascularization, or
reoperation of a valve)
- Patients undergoing cardiac surgery on CPB and having pre-operative pulmonary
hypertension due to left heart disease with systolic PAP > 60 mmHg
- Signed written informed consent
Exclusion Criteria:
- Systolic blood pressure < 100 mmHg
- Significant chronic lung disease
- Emergency surgery
- Pregnant/breast-feeding
- Investigational drug use within 28 days prior to randomization
- Complex adult congenital heart disease.
- Severe concomitant illness limiting life expectancy to < 6 months
- Participation in a device study that will affect the outcome of the study
- Pre-operative use of balloon pump, inotropes/vasopressors, treatment of pulmonary
arterial hypertension
- Known hypersensitivity to tezosentan or drugs of the same class, or any of their
excipients
- Severe liver impairment
Locations and Contacts
Medical University of Innsbruck, Innsbruck, Austria
AKH University of Vienna, Vienna, Austria
Quebec Heart Institute/Hopital Laval, Quebec G1V4G5, Canada
Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
Hopital Pitie Salpetriere, Paris, France
Deutches Herzzentrum, Berlin, Germany
Zentrum der Chirugie-Zchir-des Universitatsklinikums, Frankfurt Main 60590, Germany
Narayana Hrudayalaya, Bangalore, India
Nizam's Institute of Medical Sciences, Hyderabaad, India
Shaare Zedek Medical Center, Jerusalem, Israel
Fondazione IRCCS San Matteo Hospital, Cardiac Surgery, Pavia 27100, Italy
Azienda Sanitaria Ospedaliera "San Giovanni Battista", Cardiac Surgery Division, Torino 10126, Italy
Medical University of Silesia, 2nd Dept of Cardiac Surgery, Katowice, Poland
Klinika Chirurgii Serca, Naczyn I Transplantologii, Szpital Jana Pawla II, Krakow 31-202, Poland
Dedinje Cardiovascular Institute, Belgrade, Serbia
National Institute of Cardiovascular Diseases, Clinic of Heart Surgery, Bratslava, Slovakia
Sahlgrenska University Hospital, Goteborg, Sweden
Papworth Hospital, Cambridge, United Kingdom
Northern General Hospital, Sheffield, United Kingdom
University of Alberta Hospital, Edmonton, Alberta T6G2B7, Canada
Stanford University School of Medicine, Stanford, California 94305, United States
Dresden Universitatsklinik/Cardiology Center, Gmbh Dresden, Dresden, Germany
Columbia University Medical Center, New York, New York 10032, United States
Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York 10467, United States
Duke University Medical Center, Durham, North Carolina 27710, United States
Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, United States
The Cleveland Clinic, Cleveland, Ohio 44195, United States
London Health Sciences Centre-University Hospital, London, Ontario N6A5A5, Canada
Toronto General Hospital, Toronto, Ontario M5G2C4, Canada
Montreal Heart Institute, Montreal, Quebec H1T1C8, Canada
Baylor University Medical Center, Dallas, Texas 75226, United States
Texas Heart Institute/St. Luke's Episcopal Hospital/Baylor College, Houston, Texas 77030, United States
University of Virginia Health System, Charlottesville, Virginia 22908, United States
Additional Information
Starting date: April 2007
Last updated: February 11, 2010
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