E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute bleeding while undergoing aortic replacement surgery |
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E.1.1.1 | Medical condition in easily understood language |
Acute bleeding while undergoing aortic replacement surgery |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049052 |
E.1.2 | Term | Aortic surgery NOS |
E.1.2 | System Organ Class | 100000004865 |
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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 |
1. To assess the efficacy of FCH treatment in controlling microvascular bleeding during complex cardiovascular surgery. |
|
E.2.2 | Secondary objectives of the trial |
2. To assess the safety of FCH when used during complex cardiovascular surgery.
3. To determine the peak plasma concentration of FCH when administered during complex
cardiovascular surgery and explore its relationship with maximum clot firmness. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria:
At Screening
· Undergoing elective open surgical procedures on any part of the aorta requiring CPB, with or without other cardiac surgical procedures (e.g. valve replacement or repair, coronary artery bypass grafting, etc.).
· 18 years of age or older.
· Written informed consent for study participation obtained before undergoing any study specific procedures. Intraoperative (at the 1st 5-minute bleeding mass)
· A 5-minute bleeding mass of 60 to 250 g following discontinuation of CPB, administration of protamine, and establishment of surgical hemostasis.
· Minimum core body temperature 35°C, measured according to local practice.
· Activated clotting time ±25% of baseline levels.
· Blood pH >7.3. |
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E.4 | Principal exclusion criteria |
Exclusion Criteria:
At Screening and/or baseline
· Undergoing emergency aortic repair surgery.
· Reoperative aortic surgery at the same anatomic site as the original procedure (including resternotomy).
· Any operation for infection.
· Proof or suspicion of a congenital or acquired coagulation disorder (e.g. Von Willebrand’s disease, hemophilia or severe liver disease) or a prothrombotic disorder (e.g. protein C or S deficiency).
· Myocardial infarction (MI), acute coronary syndrome or stroke in the 2 months preceding study surgery.
· Symptomatic carotid or vertebral artery disease.
· Planned concomitant peripheral vascular procedure (e.g. carotid endarterectomy).
· Low molecular weight or unfractionated heparin in the 24 hours preceding study surgery.
· Clopidogrel administration within 5 days preceding study surgery or prasugrel administration within 7 days preceding study surgery or ticagrelor administration in the24 hours preceding study surgery.
· Factor Xa inhibitors within 2 days preceding study surgery.
· IIb/IIIa antagonist administration in the 24 hours preceding study surgery.
· Use of direct thrombin inhibitors: within 3 days preceding study surgery for dabigatran and within 24 hours preceding study surgery for all others.
· An international normalized ratio >1.3 immediately preceding the start of surgery.
· Multiple morbidities, including those that may be discovered during pre-operative evaluation, that result in an anticipated life expectancy of <6 months.
· Participation in another interventional clinical study (or use of another IMP) within 30 days before, or during, the study. Participation in an observational clinical study is permitted.
· Alcohol, drug, or medication abuse within 1 year before the study that would preclude participation and compliance with study requirements.
· Use of concomitant therapy not permitted during the study.
· Suspected inability to understand or unwillingness to comply with study procedures.
· Mental condition rendering the subject (or the subject’s legally acceptable representative[s]) unable to understand the nature, scope and possible consequences of the study.
· Known or suspected hypersensitivity to the IMP, or to any excipients of the IMP.
· Known or suspected antibodies to the IMP, or to any excipients of the IMP.
· Any condition that is likely to interfere with evaluation of the IMP or satisfactory conduct of the study.
· Employee at the study site, or spouse/partner or relative of the investigator or subinvestigators.
· Female subjects of childbearing potential either not using, or not willing to use, a medically reliable method of contraception for the entire duration of the study, or not sexually abstinent for the entire duration of the study, or not surgically sterile.
· Pregnancy or nursing mother.
· Known, active infection with hepatitis A, B, or C virus or human immunodeficiency virus-1. Intraoperative (at the 1st 5-minute bleeding mass)
· Use of any systemic hemostatic therapy (such as FFP, platelets, prothrombin complex concentrates) from the beginning of surgery until IMP administration.
· Any situation that the surgical team feels may cause participation in the study threatens the safety of the subject. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) given during the first 24 hours after administration of IMP. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of this study are the following:
· Total avoidance of allogeneic blood transfusions during the first 24 hours after administration of IMP.
· Quantity of blood loss (blood drainage volume from the chest).
· Change in 5-minute bleeding mass between the pre-treatment and the first post-treatment measurements.
· Mortality with adjudicated cause of death.
· Consumption of each individual blood product administered (FFP, platelets, and RBCs).
· Number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 6 and 12 hours after administration of IMP.
· Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered.
· Time from administration of study drug to completion of skin closure.
· A pharmacokinetic assessment consisting of determination of the peak plasma concentration of FCH, and a pharmacodynamic assessment based on the relationship between fibrinogen
exposure (Clauss and dose) and FIBTEM-measured MCF following FCH treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | No |
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 |
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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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |