E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Elective complex cardiac surgery is associated with excessive blood loss due to coagulopathy. Fibrinogen concentrate has been shown to reverse dilutional coagulopathy. In this double blinded, placebo-controlled, randomized trial we will investigate whether fibrinogen concentrate reduced blood loss and transfusion of blood products in patients experiencing excessive coagulopathic bleeding during elective complex cardiac surgery.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009802 |
E.1.2 | Term | Coagulopathy |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000531 |
E.1.2 | Term | Acquired afibrinogenaemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10005517 |
E.1.2 | Term | Blood fibrinogen |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011976 |
E.1.2 | Term | Decreased plasma fibrinogen |
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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 determine whether fibrinogen concentrate infusion reduces perioperative blood loss in patients experiencing clinically relevant microvascular bleeding during elective complex cardiac surgery. |
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E.2.2 | Secondary objectives of the trial |
To determine whether fibrinogen concentrate infusion reduces transfusion of allogenic blood products in patients experiencing clinically relevant microvascular bleeding during elective complex cardiac surgery and to determine whether its use is safe and well-tolerated. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Eighteen years of age or older. - Undergoing elective complex cardiac surgery ( CABG and valve(s) or multiple valves or aortic root, aorta ascendens or aortic arch surgery). - Understood and willingly given written informed consent (Dutch language) to participate following an explanation of study background, restrictions, and procedures. - Experience clinically relevant bleeding of the microvasculature following removal of CPB during surgery. clinically relevant microvascular bleeding defined as a 5-minute bleeding mass between 60 and 250 g and intraoperative conditions before infusion of study medication are: - Body temperature > 36°C - Blood pH > 7.3 - Hb > 5.3 mmol/L or Ht > 0.25 - ACT < 130 seconds |
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E.4 | Principal exclusion criteria |
- Positive pregnancy test, pregnancy or lactation. - Women of child-bearing age not using a medically approved method of contraception during the study. - Undergoing an emergency operation. - Proof or suspicion of a congenital or acquired coagulation disorder (e.g. VWD or via severe liver disease). - Myocardial Infarction (MI) or apoplexy in the 2 months preceding study surgery. - Manifest venous or arterial thrombosis - Use of medication: - ASA administration in the 3 days preceding surgery. - Clopidogrel administration in the 5 days preceding surgery. - Tirofiban administration in the 2 days preceding surgery. - INR >1.4 if on coumadines. - Participation in another clinical study in the 4 weeks preceding this study. - Sensitivity to any of the components of study medication. - Any indication that the restrictions or procedures of the study may not be adhered to (e.g. an uncooperative attitude). - Any indication that the study restrictions, procedures, or consequences therein have not been considered or understood, such that informed consent cannot be convincingly given. - Multiple morbidities, with a notably constrained remaining length of life.
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E.5 End points |
E.5.1 | Primary end point(s) |
Perioperative blood loss in ml measured between infusion of study medication and closure of chest.
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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 | Yes |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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
| 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 | Yes |
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
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- The trial is ended when each study arm has 60 participants, totalling 120 study participants. - The investigator has the right to discontinue this study at any time for medical or administrative reasons. The decision to discontinue the study will be based upon the risk associated with study medication outweighing its benefit. - The planned continuous sequential interim analyses will guide the decision to terminate the study prematurely. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |