Study of the Efficacy and Safety of Tezosentan in Patients With Pre-operative Pulmonary Hypertension, Due to Left Heart Disease, Undergoing Open Heart Surgery

NCT ID: NCT00458276

Last Updated: 2018-07-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 274 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2008-03-31

Brief 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.

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.

Conditions

Heart Diseases; Hypertension, Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

Tezosentan

Group Type: EXPERIMENTAL

tezosentan

Intervention Type: DRUG

Tezosentan (ACT-050089, Ro 61-0612) as a 1% solution in 0.9% NaCl (i.e., normal saline) for i.v. use.

2

Placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Placebo (i.e., normal saline) for i.v. use.

Interventions

tezosentan

Tezosentan (ACT-050089, Ro 61-0612) as a 1% solution in 0.9% NaCl (i.e., normal saline) for i.v. use.

Intervention Type: DRUG

placebo

Placebo (i.e., normal saline) for i.v. use.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andre Denault, Prof.

Role: STUDY_CHAIR

Montreal Heart Institute

Ronald Pearl, MD

Role: STUDY_CHAIR

Stanford University

Robert Michler, MD

Role: STUDY_CHAIR

Montefiore Medical Center

Steven Tsui

Role: STUDY_CHAIR

Papworth Hospital NHS Foundation Trust

Rainald Seitelberger, Prof.

Role: STUDY_CHAIR

AKH University of Vienna

Andrea D'Armini, Prof.

Role: STUDY_CHAIR

San Matteo Hospital

Locations

Stanford University School of Medicine

Stanford, California, United States

Columbia University Medical Center

New York, New York, United States

Montefiore Medical Center/Albert Einstein College of Medicine

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

The Cleveland Clinic

Cleveland, Ohio, United States

Baylor University Medical Center

Dallas, Texas, United States

Texas Heart Institute/St. Luke's Episcopal Hospital/Baylor College

Houston, Texas, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Medical University of Innsbruck

Innsbruck, , Austria

AKH University of Vienna

Vienna, , Austria

University of Alberta Hospital

Edmonton, Alberta, Canada

London Health Sciences Centre-University Hospital

London, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Quebec Heart Institute/Hopital Laval

Québec, Quebec, Canada

Institute for Clinical and Experimental Medicine (IKEM)

Prague, , Czechia

Hopital Pitie Salpetriere

Paris, , France

Deutches Herzzentrum

Berlin, , Germany

Dresden Universitatsklinik/Cardiology Center

Dresden, , Germany

Zentrum der Chirugie-Zchir-des Universitatsklinikums

Frankfurt, , 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, , Italy

Azienda Sanitaria Ospedaliera "San Giovanni Battista", Cardiac Surgery Division

Torino, , Italy

Medical University of Silesia, 2nd Dept of Cardiac Surgery

Katowice, , Poland

Klinika Chirurgii Serca, Naczyn I Transplantologii, Szpital Jana Pawla II

Krakow, , Poland

Dedinje Cardiovascular Institute

Belgrade, , Serbia

National Institute of Cardiovascular Diseases, Clinic of Heart Surgery

Bratislava, , Slovakia

Sahlgrenska University Hospital

Gothenburg, , Sweden

Papworth Hospital

Cambridge, , United Kingdom

Northern General Hospital

Sheffield, , United Kingdom

Countries

United States; Austria; Canada; Czechia; France; Germany; India; Israel; Italy; Poland; Serbia; Slovakia; Sweden; United Kingdom

References

Denault AY, Pearl RG, Michler RE, Rao V, Tsui SS, Seitelberger R, Cromie M, Lindberg E, D'Armini AM. Tezosentan and right ventricular failure in patients with pulmonary hypertension undergoing cardiac surgery: the TACTICS trial. J Cardiothorac Vasc Anesth. 2013 Dec;27(6):1212-7. doi: 10.1053/j.jvca.2013.01.023. Epub 2013 Mar 21.

Reference Type: DERIVED

PMID: 23523254 (View on PubMed)

Other Identifiers

AC-051-350

Identifier Type: -

Identifier Source: org_study_id