The Efficacy of the Administration of Fibrinogen in Liver Transplantation

Study Overview
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Brief Summary
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Objective: To evaluate the efficacy of preoperative administration of fibrinogen in liver transplantation by maintaining a preoperative plasma level equal to 2.9 g / L compared with placebo, reflecting a reduction in the number of RBC units transfused during the procedure. To determine the influence of fibrinogen administration on mortality and survival of liver graft evaluated one year after the procedure. To determine the safety of fibrinogen administration recording thrombotic complications evaluated during hospitalization or at least 30 days postoperatively.

Detailed Description
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Methods: A multicenter, randomized, double-blind, placebo-controlled study. One hundred thirty two patients (132) will randomly be assigned to: Treatment group, Fibrinogen administration; doses of fibrinogen: 1 g for an increase in the plasmatic value of fibrinogen of 0.29 g / L to obtain a value of 2.9 g / L. Placebo group, to whom the same dose volume of saline will be administered. Determinations of haematocrit, electrolytes and kidney function tests and coagulation and haemostasis and thrombelastography test are made at all stages of the proceeding. A standard protocol for intraoperative management will be applied. Blood loss, administration of blood products, fluid therapy, presence of reperfusion syndrome, operative complications and mortality and survival will be registered. Patients will be followed for one year after transplantation.

Official Title
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A Multicenter, Placebo Controlled Study to Evaluate the Efficacy of the Administration of Fibrinogen on Blood Product Requirements in Liver Transplantation

Conditions
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Intraoperative Bleeding

Intervention / Treatment
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* Drug: Fibrinogen
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients candidates for liver transplantation Patients with a value of pre-transplant plasma fibrinogen less than 2.9 g / L. Exclusion Criteria: Patients with a value of fibrinogen in the 24 hours prior to the intervention than 2.9 g / L. Known history of thromboembolic events in 30 days Known or suspected pregnancy Previous randomization in this trial Known or suspected allergy to trial products or related products Known presence of congenital bleeding disorder. Patients treated with aspirin, warfarin The following indications for transplantation: familial polyneuropathy, acute liver failure, biliary cirrhosis and sclerosing cholangitis, Budd-Chiari syndrome Heart beating donors and living donor Patient reluctant to participate in the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous Fibrinogen<br>Fibrinogen will be administered until an expected plasmatic value of 2.9 g / L is achieved. | Drug: Fibrinogen<br>* The dose of fibrinogen should be calculated at 1 g of fibrinogen in order to obtain an increase in plasma fibrinogen value of 0.29 g / L to reach a final value of 2.9 g / L. Fibrinogen ampoules powder prepared with water dilution and located in a serum at a concentration of 2g/100 ml, which will be administered by intravenous infusion for 10 minutes. Administration before surgery starts<br>* Other names: RiaSTAP;|
| Placebo Comparator: Saline Serum<br>the same dose in volume of saline dilution will be administered. The potential dose of fibrinogen required to obtain a final plasmatic reading of 2.9 g / L. will be computed. A serum will contain the corresponding ml of saline dilution | Drug: Saline<br>* the same dose in volume of water dilution will be administered. The potential dose of fibrinogen required to obtain a final plasmatic reading of 2.9 g / L. will be computed. A serum will contain the corresponding ml of water dilution. Administered before surgery starts<br>* Other names: physiologic serum;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients requiring transfusion of packed red blood cells during the procedure | record of number of red blood cell packeds transfused during the surgical procedure | intraoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients requiring blood products other than red cell concentrates | Number of packed red cells transfused during surgery Number of units of fresh frozen plasma transfused during surgery Number of platelet units transfused during surgery Grams of fibrinogen administered during surgery | intraoperative | 
| Operative outcome | Operative mortality Liver graft survival Thrombotic complications of all types and causes | 4 weeks | 
| liver transplantation outcome | Follow-up of graft survival and patient mortality one year after liver transplantation. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver, Surgery, hemostasis, coagulation, Fibrinogen