Acute bleeding while undergoing aortic replacement surgery MedDRA version: 16.1 Level: LLT Classification code 10049052 Term: Aortic surgery NOS System Organ Class: 100000004865
Conditions
Interventions
Trade Name: Riastap 1g, Haemocomplettan P 1g
Product Name: Fibrinogen Concentrate
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Human Fibrinogen
CAS Number: 900
Sponsors
CSL Behring GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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 76 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
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 such as replacement of a previously placed aortic graft. Resternotomy and rethoracotomy are permitted. · 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the efficacy of FCH treatment in controlling microvascular bleeding during complex cardiovascular surgery.;Secondary Objective: 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.;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.;Timepoint(s) of evaluation of this end point: First 24h | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;Timepoint(s) of evaluation of this end point: See Protocol | — |
Countries
Austria, Brazil, Canada, Czech Republic, Denmark, Finland, Germany, India, Italy, Poland, United Kingdom
Contacts
Public ContactDirk Steffen Schmidt
CSL Behring GmbH
Outcome results
None listed