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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


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 therapy

Time 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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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


- 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

Page last updated: August 23, 2015

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