The Efficacy of the Administration of Fibrinogen in Liver Transplantation (FibstudLT)

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

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.

Study Overview

• Status: Unknown
• Conditions: Intraoperative Bleeding
• Intervention / Treatment: Drug: Fibrinogen; Drug: Saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Murcia, Spain
    • Hospital Virgen de la Arrixaca
  • Sevilla, Spain
    • Hospital Virgen del Rocío
  • Vizcaya
    • Bilbao, Vizcaya, Spain
      • Hospital de Cruces

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intravenous Fibrinogen; Fibrinogen will be administered until an expected plasmatic value of 2.9 g / L is achieved.	Drug: Fibrinogen; 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; Other Names: Haemocomplettan; RiaSTAP
PLACEBO_COMPARATOR: Saline Serum; 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; 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; Other Names: physiologic serum

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Universitari de Bellvitge
• Collaborators: Spanish Clinical Research Network - SCReN
• Investigators: Study Director: Antoni Sabate, MD, Hospital Universitari Bellvitge.IDIBELL

Publications and helpful links

General Publications

• Blasi A, Sabate A, Beltran J, Costa M, Reyes R, Torres F. Correlation between plasma fibrinogen and FIBTEM thromboelastometry during liver transplantation: a comprehensive assessment. Vox Sang. 2017 Nov;112(8):788-795. doi: 10.1111/vox.12598. Epub 2017 Oct 8.
• Sabate A, Gutierrez R, Beltran J, Mellado P, Blasi A, Acosta F, Costa M, Reyes R, Torres F. Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Am J Transplant. 2016 Aug;16(8):2421-9. doi: 10.1111/ajt.13752. Epub 2016 Mar 17.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ANTICIPATED): January 1, 2015

Study Registration Dates

• First Submitted: February 2, 2012
• First Submitted That Met QC Criteria: February 21, 2012
• First Posted (ESTIMATE): February 27, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 4, 2014
• Last Update Submitted That Met QC Criteria: December 3, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Surgery; Liver; hemostasis; coagulation; Fibrinogen
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Intraoperative Complications; Blood Loss, Surgical
• Other Study ID Numbers: Promotor Code 1553-H-459; 2010-024584-41 (EUDRACT_NUMBER)