Study of the Efficacy and Safety of Tezosentan in Patients With Pre-operative Pulmonary Hypertension, Due to Left Heart Disease, Undergoing Open Heart 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 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|
- 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 ]
- 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 ]
|Study Start Date:||April 2007|
|Study Completion Date:||March 2008|
|Primary Completion Date:||February 2008 (Final data collection date for primary outcome measure)|
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 (i.e., normal saline) for i.v. use.
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.
Show 33 Study Locations
|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|