Impact of Two Guided Transfusion Strategies on Blood Product Requirements in Liver Transplantation.

Impact of Two Thromboelastometry-guided Transfusion Strategies on Blood Product Requirements in Liver Transplantation. a Multicenter, Randomized Trial. TROMBOFIBtrial

It is a national multicentre clinical study, where 3 hospitals are involved: Bellvitge University Hospital, Clinic Hospital of Barcelona and Cruces Hospital of Bilbao). It is a randomized study based on the Hemoglobin value of the patient with a 1:1 ratio, parallel groups, controlled and single blind, in patients undergoing an orthotopic liver transplant, confirming previously that the participants fulfill all the inclusion criteria and none of exclusion.

Study Overview

• Status: Active, not recruiting
• Conditions: Fibrin Blood Clot
• Intervention / Treatment: Drug: Fibrinogen Concentrate (Human) 1 MG [RiaSTAP]

Detailed Description

A total of 176 patients will be included (88 per group) and each center can not include more than 40% of the sample to avoid bias.

Blood samples will be analyzed at different times of the surgical intervention by an electronic device called thromboelastogram. It evaluates the blood clot characteristics and, depending on the results, assesses the need to correct values by the administration of fibrinogen or platelets.

One of the coagulation parameter evaluated and corrected by thromboelastogram is called A10FIBTEM. In a previous study, the investigators have seen that maintaining some specific ranges in the A10FIBTEM, results in a decrease of the use of blood products. That's why the investigators have created 2 groups:

• The control group will be corrected up to a value of A10FIBTEM = 8mm.
• The intervention group will be corrected up to a value of A10FIBTEM = 11mm.

Subsequently, results between groups will be compared. The investigators have to consider that the drug used in this study (Riastap) is an authorized and commercial drug.

The main objective is to demonstrate that the administration of fibrinogen in the intervention group compared to the control group changes the administration of red blood cells pack during the liver transplant and in the first 24 hours after.

Secondary objectives consist in demonstrate that in the intervention group, there is also a change in the administration of other blood products, a change in acute renal damage, a change in hours of mechanical ventilation, no changes in thrombotic events in the hepatic graft or in the patient in the first 90 days of the liver transplant and no changes in re operations, re-transplantation, or mortality during the first 90 days of the liver transplant, compared to the control group.

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Clinic Hospital
  • Barcelone
    • Hospitalet de Llobregat, Barcelone, Spain, 08907
      • Bellvitge Universitary Hospital
  • Vizcaya
    • Bilbao, Vizcaya, Spain
      • Cruces Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years.
• Candidate to an orthotopic liver trasnplantation.
• Informed consent.
• Preoperative hemoglobine </= 130 g/L

Exclusion Criteria:

• Preoperative hemoglobin> 130 g / L
• Familial amyloid polyneuropathy
• Polycystosis hepatic
• Living donor liver transplant
• Uncontrolled donor after cardiac death
• Acute / subacute liver failure
• Re-transplant (in the same hospital admission)
• Use of Anticoagulation drugs before transplantation.
• Age <18 years.
• Pregnancy and lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; The doses of fibrinogen will be calculated acording to the formula based on previous study (AJT2017), rounded to the higher value according to the presentation format of the drug. Study medication will be stored at the hospital pharmacy. Formula: 8mm - A10FIBTEM registered in mm) x 1.1 = fibrinogen dose required	Drug: Fibrinogen Concentrate (Human) 1 MG [RiaSTAP]; The drug used in this study is Riastap, 1g (Fibrinogen). The dose administered will depend on the arm group assigned and in the results of the thromboelastogram during the procedure.
Experimental: intervention group; The doses of fibrinogen will be calculated acording to the formula based on previous study (AJT2017), rounded to the higher value according to the presentation format of the drug. Study medication will be stored at the hospital pharmacy. Formula: 11mm - A10FIBTEM registered in mm) x 1.1 = fibrinogen dose required	Drug: Fibrinogen Concentrate (Human) 1 MG [RiaSTAP]; The drug used in this study is Riastap, 1g (Fibrinogen). The dose administered will depend on the arm group assigned and in the results of the thromboelastogram during the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the rate of red blood cell packs transfusion during procedure and in the first 24hours after between groups.	Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10FIBTEM value of 11mm, change the administration of red blood cell pack during the procedure and in the first 24 hours after it, comparing to the administration of fibrinogen up to an A10FIBTEM of 8mm.	Intraoperative and the first 24 hours after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the rate of other blood products between groups.	Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the administration of platelets, frozen fresh plasma and other blood products.	Intraoperative and the first 24 hours after surgery.
Evaluation of the acute kidney injury between groups using the Kidney Disease Improving Global Outcomes scale,the minimum values is 1 and the maximum values is 3, higher scores mean a worse outcome.	Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the kidney injury through study completion	first week after the procedure and until 90 days after the procedure.
Evaluation of the duration of mechanical ventilation in hours between groups.	Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the need of mechanical ventilation through study completion (comparing the number of hours of mechanical ventilation of each group).	first week after the procedure and until 90 days after the procedure..
Number of participants with major advers cardiac events (MACE), Number of participants with, any sign of infection, Number of participants with neurological events through study completion	Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm change the Number of participants with any adverse events.	Until 90 days after the procedure.
Number of participants with thrombotic events in the hepatic graft measured by ecodoppler assessment; and the number of participants with any other thrombotic events measured by ecodoppler assessment of leg extremity or tomography axial of the lungs	Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm do not change thrombotic events in the hepatic graft or in the patient.	Until 90 days after procedure
Number of participants who require reoperation for any cause; Number of participants who require being re transplanted and number of participant who died through the study completion	Demonstrate that the A10FIBTEM correction with the administration of fibrinogen up to an A10 FIBTEM value of 11mm do not change the outcome related to reoperation, re-transplantations or mortality.	Until 90 days after procedure

Collaborators and Investigators

• Sponsor: Antoni Sabaté Pes
• Investigators: Principal Investigator: Marta Caballero, Bellvitge University Hospital; Principal Investigator: Josep Beltran, Clinic Hospital, Barcelona; Principal Investigator: Rosa Gutierrez, Cruces Hospital, Bilbao

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2019
• Primary Completion (Actual): November 2, 2021
• Study Completion (Anticipated): October 31, 2022

Study Registration Dates

• First Submitted: October 10, 2019
• First Submitted That Met QC Criteria: May 22, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Actual): November 26, 2021
• Last Update Submitted That Met QC Criteria: November 24, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: orthotopic liver transplantation; fibrinogen; red blood cell pack transfusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis
• Other Study ID Numbers: TROMBOFIBtrial; 2018-002510-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No