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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 274
- 试验地点
- 33
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
1
Tezosentan
干预措施: tezosentan (Drug)
2
Placebo
干预措施: placebo (Drug)
结局指标
主要结局
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.
时间窗: During weaning from CPB
次要结局
- 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)