E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Separation from cardiopulmonary by-pass |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039163 |
E.1.2 | Term | Right ventricular failure |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
1) To evaluate the effect of tezosentan on the incidence of major clinical events up to 28 days after study drug start. 2) To evaluate the effect of tezosentan on the time to weaning off cardiopulmonary bypass and time to discharge from intensive care unit 3)To evaluate the tolerability and safety of tezosentan in this patient population. |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Patients οΎ³ 18 years of age 2) Male or female patients (females of child-bearing potential must have been surgically sterilized or use a reliable method of contraception) 3) Patients undergoing complex cardiac surgery on CPB and having sPAP > 40 mmHg or mPAP > 30 mmHg (measured at screening by RHC or echocardiography) or patients undergoing cardiac surgery on CPB and having pre-operative pulmonary hypertension due to left heart disease (measured at screening by RHC or echocardiography) defined as sPAP > 60 mmHg with mPAP/MAP > 0.5 or sPAP > 60 mmHg with signs and/or symptoms of right ventricular dysfunction 4) Signed informed consent prior to any study-mandated procedure. |
|
E.4 | Principal exclusion criteria |
1) Sitting systolic blood pressure < 100 mmHg (measured at hospital admission) 2) Significant chronic lung disease that might interfere with the ability to interpret the study results (e.g., severe chronic obstructive pulmonary disease).3) Emergency surgery 4) Pregnant or breast-feeding females 5) Use of another investigational drug within 28 days prior to randomization 6) Complex adult congenital heart disease 7) Severe concomitant illness limiting life expectancy (< 6 months) 8) Participation in a device study that will affect the outcome of the study 9) Pre-operative use of balloon pump 10) Pre-operative use of inotropes/vasopressor drugs 11) Pre-operative treatment of pulmonary arterial hypertension (PAH) 12) Known hypersensitivity to tezosentan or drugs of the same class, or any of their excipients 13) Severe liver impairement |
|
E.5 End points |
E.5.1 | 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) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |