Study of Fibrinogen Concentrate (Human) (FCH) to Control Bleeding During Complex Cardiovascular Surgery

CSL Behring152 enrolled

Overview

The purpose of this study is to demonstrate that Fibrinogen Concentrate (Human)(FCH) can reduce the amount of donor blood products needed during complex cardiovascular surgery, and that it is safe and well tolerated. Subjects in this study will get either a FCH or placebo infusion during surgery. This will be in addition to the standard treatment, which is donor blood or blood products. Placebo does not contain any effective medicine. The study is randomised. This means that the likelihood that subjects will get FCH or placebo is 50%. To make the comparison between FCH and placebo as fair as possible, the study is "double blind". This means that neither the subjects nor the study doctor will know if FCH or placebo is administered. If necessary, the study doctor can find out which treatment the subjects are receiving.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

152

Conditions

Surgical Blood Loss Postoperative Blood Loss

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: At Screening: * Undergoing elective open surgical procedures on any part of the aorta requiring cardiopulmonary bypass (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. 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. * 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 the 48 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. 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.

Locations (35)

Allgemeines Krankenhaus der Stadt Wien - Universitätskliniken

Vienna, Austria

Fundacao Universitaria de Cardiologia - Instituto de Cardiol

Porto Alegre, Rio Grande do Sul, Brazil

InCor

São Paulo, São Paulo, Brazil

Providence Health-St Paul's Hospital

Vancouver, British Columbia, Canada

Hamilton Health Science

Hamilton, Ontario, Canada

Outcomes

Primary Outcomes

Total units of allogeneic blood products

Number of units administered of all allogeneic blood products combined (fresh frozen plasma, platelets, and red blood cells)

Time frame: Up to 24 hours after investigational medicinal product (IMP) administration

Secondary Outcomes

Total avoidance of allogeneic blood transfusions

Number of subjects who are alive and do not have any administration of platelets, fresh frozen plasma (FFP), and red blood cells (RBCs) during the first 24 hours after administration of IMP

Time frame: 24 hours after IMP administration

Quantity of blood loss (6 hours)

Blood drainage volume from the chest

Time frame: 6 hours after skin closure

Quantity of blood loss (12 hours)

Blood drainage volume from the chest

Time frame: 12 hours after skin closure

Quantity of blood loss (24 hours)

Blood drainage volume from the chest

Time frame: 24 hours after skin closure

Change in bleeding mass

The 5-minute bleeding mass is measured as the difference in weight of surgical swabs after 5 minutes of surgical packing of the aortic surgical site.

Time frame: Immediately before and 5 minutes after completion of IMP administration

Mortality (Day 10)

Mortality with adjudicated cause of death up to 10 days after surgery

Time frame: Up to 10 days after surgery

Mortality (Day 30)

Mortality with adjudicated cause of death up to 30 days after surgery

Time frame: Up to 30 days after surgery

FFP consumption (24 hours)

Time frame: 24 hours after IMP administration

FFP consumption (10 days)

Time frame: 10 days after IMP administration

Platelet consumption (24 hours)

Time frame: 24 hours after IMP administration

Platelet consumption (10 days)

Time frame: 10 days after IMP administration

Red blood cells (RBC) consumption (24 hours)

Time frame: 24 hours after IMP administration

RBC consumption (10 days)

Time frame: 10 days after IMP administration

Total units of all allogeneic blood products (6 hours)

Number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 6 hours after administration of IMP

Time frame: 6 hours after IMP administration

Total units of all allogeneic blood products (12 hours)

Number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 12 hours after administration of IMP

Time frame: 12 hours after IMP administration

Volume of all allogeneic blood products (6 hours)

Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 6 hours after administration of IMP

Time frame: 6 hours after IMP administration

Volume of all allogeneic blood products (12 hours)

Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 12 hours after administration of IMP

Time frame: 12 hours after IMP administration

Volume of all allogeneic blood products (24 hours)

Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 24 hours after administration of IMP

Time frame: 24 hours after IMP administration

Time from administration of study drug to completion of skin closure

Time frame: Average 2 hours

Mortality (24 hours)

Mortality with adjudicated cause of death during the first 24 hours after administration of IMP

Time frame: WIthin 24 hours after IMP administration

Peak plasma concentration of fibrinogen (Cmax)

Time frame: At up to 10 time points from baseline and up to Day 11 after surgery.

Maximum clot firmness

Time frame: At baseline; on the day of surgery at: 30 min before CPB, the 1st 5 min bleeding mass, the end of IMP infusion, the 2nd 5-min bleeding mass, and closure; and on Day 2, 3, 4 and at the end of the study (discharge/Day 11 or at discontinuation if earlier).