REPLACE (Randomized evaluation of fibrinogen versus placeboin complex cardiovascular surgery): a prospective, multinational,multicenter, randomized, double-blind, placebo-controlled, phaseIII study for the use of Fibrinogen Concentrate (Human) (FCH) incomplex cardiovascular surgery
- Conditions
- Acute bleeding while undergoing aortic replacement surgeryMedDRA version: 16.1Level: LLTClassification code 10049052Term: Aortic surgery NOSSystem Organ Class: 100000004865Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2011-002685-20-DE
- Lead Sponsor
- CSL Behring GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 152
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:
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.<br>3. To determine the peak plasma concentration of FCH when administered during complex<br>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 Outcome Measures
Name Time Method