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

July 6, 2018 updated by: Idorsia Pharmaceuticals Ltd.

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

274

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria
        • Medical University of Innsbruck
      • Vienna, Austria
        • AKH University of Vienna
  • Canada
      • Quebec, Canada, G1V4G5
        • Quebec Heart Institute/Hopital Laval
    • Alberta
      • Edmonton, Alberta, Canada, t6g2b7
        • University of Alberta Hospital
    • Ontario
      • London, Ontario, Canada, N6A5A5
        • London Health Sciences Centre-University Hospital
      • Toronto, Ontario, Canada, M5G2C4
        • Toronto General Hospital
    • Quebec
      • Montreal, Quebec, Canada, H1T1C8
        • Montreal Heart Institute
  • Czechia
      • Prague, Czechia
        • Institute for Clinical and Experimental Medicine (IKEM)
  • France
      • Paris, France
        • Hopital Pitie Salpetriere
  • Germany
      • Berlin, Germany
        • Deutches Herzzentrum
      • Dresden, Germany
        • Dresden Universitatsklinik/Cardiology Center
      • Frankfurt, Germany, Main 60590
        • Zentrum der Chirugie-Zchir-des Universitatsklinikums
  • India
      • Bangalore, India
        • Narayana Hrudayalaya
      • Hyderabaad, India
        • Nizam's Institute of Medical Sciences
  • Israel
      • Jerusalem, Israel
        • Shaare Zedek Medical Center
  • Italy
      • Pavia, Italy, 27100
        • Fondazione IRCCS San Matteo Hospital, Cardiac Surgery
      • Torino, Italy, 10126
        • Azienda Sanitaria Ospedaliera "San Giovanni Battista", Cardiac Surgery Division
  • Poland
      • Katowice, Poland
        • Medical University of Silesia, 2nd Dept of Cardiac Surgery
      • Krakow, Poland, 31-202
        • Klinika Chirurgii Serca, Naczyn I Transplantologii, Szpital Jana Pawla II
  • Serbia
      • Belgrade, Serbia
        • Dedinje Cardiovascular Institute
  • Slovakia
      • Bratislava, Slovakia
        • National Institute of Cardiovascular Diseases, Clinic of Heart Surgery
  • Sweden
      • Goteborg, Sweden
        • Sahlgrenska University Hospital
  • United Kingdom
      • Cambridge, United Kingdom
        • Papworth Hospital
      • Sheffield, United Kingdom
        • Northern General Hospital
  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10467
        • Montefiore Medical Center/Albert Einstein College of Medicine
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • The Cleveland Clinic
    • Texas
      • Dallas, Texas, United States, 75226
        • Baylor University Medical Center
      • Houston, Texas, United States, 77030
        • Texas Heart Institute/St. Luke's Episcopal Hospital/Baylor College
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 2
Placebo
Drug: placebo
Placebo (i.e., normal saline) for i.v. use.
Experimental: 1
Tezosentan
Drug: tezosentan
Tezosentan (ACT-050089, Ro 61-0612) as a 1% solution in 0.9% NaCl (i.e., normal saline) for i.v. use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: During weaning from CPB
During weaning from CPB

Secondary Outcome Measures

Outcome Measure
Time Frame
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 Frame: Within 28 days after study initiation
Within 28 days after study initiation
Time to weaning from cardiopulmonary bypass
Time Frame: Defined as time from release of cross-clamp to successful weaning from CPB
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)
Time Frame: From end of CPB to final discharge from ICU
From end of CPB to final discharge from ICU

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Idorsia Pharmaceuticals Ltd.

Investigators

  • Study Chair: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

February 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

April 6, 2007

First Submitted That Met QC Criteria

April 6, 2007

First Posted (Estimate)

April 10, 2007

Study Record Updates

Last Update Posted (Actual)

July 9, 2018

Last Update Submitted That Met QC Criteria

July 6, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-051-350

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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