Cardiac Surgery, Separation from cardiopulmonary bypass MedDRA version: 9.1 Level: LLT Classification code 10063082 Term: Acute right ventricular failure
Conditions
Interventions
Product Name: Tezosentan
Product Code: ACT-050089 (Ro 61-0612)
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: Tezosentan dissodium
CAS Number: 180384-58-0
Current Sponsor code: ACT-050
Sponsors
Actelion Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion 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). Females can only participate in the study if they are postmenopausal, naturally amenorrheic for at least 1 year, surgically sterile or practicing a reliable method of contraception. Reliable methods of contraception, which must be used for the entire duration of the study and for at least 3 months after last study drug intake are: ·Intrauterine devices ·Oral, injectable, transdermal or implantable hormonal contraceptives only in combination with a barrier method (e.g., female condom, diaphragm, contraceptive sponge) or use of a condom by her partner. ·Hormone-based contraceptives alone, regardless of the route of administration, are not considered as reliable methods of contraception. ·Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception. ·Patients undergoing complex* cardiac surgery on CPB and having sPAP > 40 mmHg or mPAP > 30 mmHg (measured by RHC or echocardiography at screening). * Complex cardiac surgery is defined as: o Surgery on two valves o Surgery on one valve plus revascularization o Re-operation of previous valve surgery. Or Patients undergoing cardiac surgery on CPB and having pre-operative pulmonary hypertension due to left heart disease (measured by RHC or echocardiography at screening) defined as o sPAP > 60 mmHg with mPAP/MAP > 0.5 or o sPAP > 60 mmHg with signs and/or symptoms of right ventricular dysfunction. · Signed informed consent prior to any study-mandated procedure. MAP = mean arterial pressure; mPAP = mean pulmonary arterial pressure; sPAP = systolic pulmonary arterial pressure; RHC = right heart catheterization. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: · Sitting systolic blood pressure < 100 mmHg (measured at hospital admission). · Significant chronic lung disease that might interfere with the ability to interpret the study results (e.g., severe chronic obstructive pulmonary disease). · Emergency surgery. · Pregnant or breast-feeding females. · Use of another investigational drug within 28 days prior to randomization. · Complex adult congenital heart disease. · Severe concomitant illness limiting life expectancy (< 6 months). · Participation in a device study that will affect the outcome of the study. · Pre-operative use of balloon pump. · Pre-operative use of inotropes/vasopressor drugs. · Pre-operative treatment of pulmonary arterial hypertension (PAH). · Known hypersensitivity to tezosentan or drugs of the same class, or any of their excipients. · Severe liver impairment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that tezosentan, in patients undergoing cardiac surgery with cardiopulmonary bypass, reduces the incidence of clinically relevant right ventricular failure resulting in difficult separation from bypass or need for return to cardiopulmonary bypass or use of ventricular assist device or death.;Secondary Objective: · To evaluate the effect of tezosentan on the incidence of major clinical events up to 28 days after study drug start. · To evaluate the effect of tezosentan on the time to weaning off cardiopulmonary bypass and time to final discharge from intensive care unit (ICU). · To evaluate the tolerability and safety of tezosentan in this patient population.;Primary end point(s): Proportion of patients during weaning from CPB, with clinically relevant right ventricular failure defined as absence of or significant reduction of right ventricular wall motion by direct visual inspection peri-operatively and/or severe reduction of right ventricular fraction area change (>20%) measured by 2-D echocardiography, requiring the use of 3 or more inotropic/vasopressor treatments or 2 at high doses*, return to CPB, use of rescue therapy for high PAP, use of ventricular assist device or with fatal outcome (all causes, up to 24 hours after start of weaning). *Definition of high dose of vasopressor/inotropic drugs: · Dopamine > 5 ug/kg/min · Dobutamine > 5ug/kg/min · Norepinephrine (noradrenalin) > 0.05 ug/kg/min · Epinephrine (adrenalin) > 0.05 mg/kg/min · Milrinone bolus >= 50 ug/kg, and > 0.5 ug/kg/min · Phenylephrine > 2.5 ug/kg/min · Isoproterenol > 0.01 ug/min · Vasopressin at a cumulative dose of > 10 units · Levosimendan >= 0.2 ug/kg/min | — |
Countries
Austria, Czech Republic, France, Germany, Italy, Sweden, United Kingdom
Outcome results
None listed