E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This trial will involve approximately 42 patients requiring coronary artery bypass graft surgery (CABG). |
|
MedDRA Classification |
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 |
The primary objective of this trial is to characterise the conditions for the elimination of bivalirudin through the use of zero balanced modified ultra-filtration (ZBMUF) after separation from cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass graft surgery (CABG). An additional objective of the study is to understand the effect of high dose aprotinin during constant bivalirudin infusion after CPB under standardised conditions. |
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Provide written informed consent before the initiation of any study related procedures. • Be at least 18 years of age. • Be scheduled for a non-emergent CABG, CABG and single valve surgery, or isolated single valve surgery on CPB under normothermic conditions. Patients undergoing repeat CABG or repeat single valve are also eligible for this study. • Have a creatinine clearance > 30 ml/min • Have a left ventricular ejection fraction > 30%.
|
|
E.4 | Principal exclusion criteria |
Patients will not be included in this study if they have or have had: • A cerebrovascular accident within 6 months or any cerebrovascular accident with a residual neurological deficit. • A confirmed pregnancy at time of enrollment. (Women of child bearing potential must have a negative urine or serum pregnancy test prior to enrolment, nursing mothers will also be excluded. Women of childbearing potential must use an acceptable form of birth control (oral contraceptives or estrogen-eluting intrauterine device)). • An intracranial neoplasm, arteriovenous malformation or aneurysm. • A dependency on renal dialysis or creatinine clearance <30ml/min. • Poor left ventricular function (ejection fraction < 30%). • Ongoing treatment with warfarin (or another oral anticoagulant) at the time of enrollment or warfarin within 5 days of enrollment. • Treatment with Dextran. • Known allergy to bivalirudin or hirudin-derived drugs, or known sensitivity to any component of the product. • Received clopidogrel (Plavix®)within the previous 5 days of enrollment. • Received a glycoprotein IIb/IIIa inhibitor within the previous 48 hours if abciximab (ReoPro®) or 24 hours if eptifibatide (Integrilin®) or tirofiban (Aggrastat®) of enrollment. • Received LMWH or thrombolytics within the previous 12 hours or unfractionated heparin within 30 minutes of enrollment unless aPTT < 50 sec or ACT <175 sec. • Participated in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment, and/or are enrolled in another investigational drug study that has not completed the follow-up phase. • Received lepirudin (Refludan®), argatroban (Novostan®), Desirudin (Revasc®), and Danaparoid (Orgaran®) within the previous 24 hours prior to enrollment. • Refused to undergo blood transfusion should it become necessary. • Any other disease or condition, which, in the judgment of the Investigator, would place a patient at undo risk by being enrolled in the trial, or cause inability to comply with the trial. • Planned surgical procedure in which proximal anastomoses will precede distal anastomoses of the bypass grafts. • Planned (>1) double (or greater) valve repair-replacement (e.g.: AVR-MVR) surgery. • Known allergy to aprotinin (Trasylol®), or known sensitivity to any component of the product. • Received aprotinin (Trasylol®) within the previous 6 months of enrollment. Patients excluded for any of the above reasons may be re-screened for participation at any time if the exclusion characteristic has changed. - Active bleeding or increased risk of bleeding due to hemostasis disorders and/or irreversible coagulation disorders -Severe uncontrolled hypertension and subacute bacterial endocarditis
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
This is a pharmacokinetic study. The criteria for evaluation are:
• plasma levels of bivalirudin during constant infusion termination and separation from CPB. • The effectiveness of post-operative hemofiltration on bivalirudin elimination. • Functional assessments of anticoagulation during and after CPB. • Bivalirudin plasma levels during high dose aprotinin administration during and after CPB independent of any influence from hemofiltration. • Duration of surgery, duration of CPB and time from end of CPB to skin closure or end of surgery will be assessed.
|
|
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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
|
Patient follow up will continue until day 7 or discharge, whichever occurs first. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |