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

Idorsia Pharmaceuticals

Status and phase

Terminated

Phase 3

Conditions

Hypertension, Pulmonary

Heart Diseases

Treatments

Drug: placebo

Drug: tezosentan

Study type

Interventional

Funder types

Industry

Identifiers

NCT00458276

AC-051-350

Details and patient eligibility

About

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.

Full 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.

Enrollment

274 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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