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

NCT00458276 | Terminated Phase 3 DMC

• 1 other identifier: AC-051-350
• Study Type: interventional
• Target: 274
• Locations: 13 countries
• Sites: 32

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.

Conditions

Heart Diseases; Hypertension, Pulmonary

Keywords

Left sided heart disease; Elevated pulmonary arterial pressure; Right ventricular failure; Cardiac surgery; heart-lung machine; cardiopulmonary bypass; tezosentan; Actelion

Outcome Measures

Primary Outcomes (1)

• 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.

  During weaning from CPB

Secondary Outcomes (3)

• 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

  Within 28 days after study initiation

• Time to weaning from cardiopulmonary bypass

  Defined as time from release of cross-clamp to successful weaning from CPB

• Time from end of CPB to final discharge from Intensive Care Unit (ICU)

  From end of CPB to final discharge from ICU

Study Arms (2)

1

EXPERIMENTAL

Tezosentan

Drug: tezosentan

2

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

tezosentan DRUG

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

1

placebo DRUG

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

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (33)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore Medical Center/Albert Einstein College of Medicine

New York, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Baylor University Medical Center

Dallas, Texas, 75226, United States

Location

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

Houston, Texas, 77030, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Medical University of Innsbruck

Innsbruck, Austria

Location

AKH University of Vienna

Vienna, Austria

Location

University of Alberta Hospital

Edmonton, Alberta, T6G2B7, Canada

Location

London Health Sciences Centre-University Hospital

London, Ontario, N6A5A5, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G2C4, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T1C8, Canada

Location

Quebec Heart Institute/Hopital Laval

Québec, Quebec, G1V4G5, Canada

Location

Institute for Clinical and Experimental Medicine (IKEM)

Prague, Czechia

Location

Hopital Pitie Salpetriere

Paris, France

Location

Deutches Herzzentrum

Berlin, Germany

Location

Dresden Universitatsklinik/Cardiology Center

Dresden, Germany

Location

Zentrum der Chirugie-Zchir-des Universitatsklinikums

Frankfurt, Main 60590, Germany

Location

Narayana Hrudayalaya

Bangalore, India

Location

Nizam's Institute of Medical Sciences

Hyderabaad, India

Location

Shaare Zedek Medical Center

Jerusalem, Israel

Location

Fondazione IRCCS San Matteo Hospital, Cardiac Surgery

Pavia, 27100, Italy

Location

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

Torino, 10126, Italy

Location

Medical University of Silesia, 2nd Dept of Cardiac Surgery

Katowice, Poland

Location

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

Krakow, 31-202, Poland

Location

Dedinje Cardiovascular Institute

Belgrade, Serbia

Location

National Institute of Cardiovascular Diseases, Clinic of Heart Surgery

Bratislava, Slovakia

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Papworth Hospital

Cambridge, United Kingdom

Location

Northern General Hospital

Sheffield, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23523254 DERIVED

MeSH Terms

Conditions

Heart Diseases; Hypertension, Pulmonary; Heart Failure

Interventions

tezosentan

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

Study Officials

• Andre Denault, Prof.

  Montreal Heart Institute

  STUDY CHAIR

• Ronald Pearl, MD

  Stanford University

  STUDY CHAIR

• Robert Michler, MD

  Montefiore Medical Center

  STUDY CHAIR

• Steven Tsui

  Papworth Hospital NHS Foundation Trust

  STUDY CHAIR

• Rainald Seitelberger, Prof.

  AKH University of Vienna

  STUDY CHAIR

• Andrea D'Armini, Prof.

  San Matteo Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2007
• First Posted: April 10, 2007
• Study Start: April 1, 2007
• Primary Completion: February 1, 2008
• Study Completion: March 1, 2008
• Last Updated: July 9, 2018

Record last verified: 2018-07

Locations

PL (2); SE (1); GB (2); AU (2); IT (2); CZ (1); FR (1); US (9); SL (1); CA (5); IN (2); DE (3); IL (1)