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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

This study has been terminated.
(6 month vital status report not collected after 28 day follow up analysis indicated no difference between placebo & tezosentan)
Sponsor:
Information provided by:
Actelion
ClinicalTrials.gov Identifier:
NCT00458276
First received: April 6, 2007
Last updated: February 11, 2010
Last verified: February 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Heart Diseases
Hypertension, Pulmonary
 Drug: tezosentan
Drug: placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Actelion:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Time to weaning from cardiopulmonary bypass [ Time Frame: Defined as time from release of cross-clamp to successful weaning from CPB ] [ Designated as safety issue: No ]
  • Time from end of CPB to final discharge from Intensive Care Unit (ICU) [ Time Frame: From end of CPB to final discharge from ICU ] [ Designated as safety issue: No ]
Enrollment: 274
Study Start Date: April 2007
Study Completion Date: March 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Placebo Comparator: 2
Placebo
 Drug: placebo
Placebo (i.e., normal saline) for i.v. use.

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
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00458276

  Show 33 Study Locations
Sponsors and Collaborators
Actelion
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
Study Chair: Rainald Seitelberger, Prof. AKH University of Vienna
Study Chair: Andrea D'Armini, Prof. San Matteo Hospital
  More Information

No publications provided by Actelion

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Elisabet Lindberg, MD, International Clinical Leader, Actelion
ClinicalTrials.gov Identifier: NCT00458276     History of Changes
Other Study ID Numbers: AC-051-350
Study First Received: April 6, 2007
Last Updated: February 11, 2010
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Heart Diseases
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
 Vascular Diseases
Tezosentan
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on March 03, 2015