Fibrinogen in Liver Transplant Subjects

Early Phase 1

Not yet recruiting

• Conditions: Liver Transplant Surgery
• Interventions: Biological: Cryoprecipitate Antihemophilic Factor (AHF); Biological: Cryoprecipitate Intercept Fibrinogen Complex (IFC)

• Registration Number: NCT06764927
• Lead Sponsor: Ezeldeen Abuelkasem

Brief Summary

The study is a prospective, multi-centered, unblinded, randomized controlled pilot study. The primary objective is to compare functional hemostatic capacity of Investigational Cryoprecipitate Intercept Fibrinogen Complex (IFC) to Standard Cryoprecipitate Antihemophilic Factor (AHF) for liver transplant patients with bleeding and hypofibrinogenemia to determine impact of earlier access to a concentrated source of fibrinogen in a goal-directed manner.

Detailed Description

Fibrinogen is an important factor for hemostasis and when it is deficient or dysfunctional replacing it will improve hemostasis and reduce bleeding. Observational data indicates the use of cryoprecipitate as a source of fibrinogen may reduce bleeding and improve outcomes in patients with severe bleeding. Liver transplant patients often become hypofibrinogenemic and may benefit from early goal directed use of cryoprecipitate or IFC. IFC can be more readily available since it can be stored at room temperature compared to cryoprecipitate which requires thawing. As a result, IFC can be immediately available when indicated compared to the delay in administration of cryoprecipitate due to the need for it to be thawed. This trial will compare clinical outcomes for subjects randomized to either cryoprecipitate or IFC in bleeding liver transplant patients with reduced fibrinogen function.

There is no data comparing outcomes for subjects receiving IFC or cryoprecipitate in any patient population.

The rationale for this trial is to compare IFC to cryoprecipitate (cryo) to assist with the design of a future definitice multicenter trial. Potential advantages of IFC are that since it is stored at room temperature it can be made immediatwlt available whereas with cryo the delay in treatment can be 30 to 40 min due to the need to thaw it from a frozen state. The reduced time to treatment of bleeding may improve outcomes with the use of IFC compared to cryo. In vitro data indicates similar hemostatic function between IFC and Cryo. IFC is pathogen reduced cryoprecipitate. The pathogen reduction methods are licensed for IFC and there has been no safety concerns regarding its use at the centers that are currently using it as their standard product (unpublished).

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-18
• Study First Submitted QC: 2025-01-07
• Last Update Submitted: 2025-01-07
• Study First Posted: 2025-01-09
• Last Update Posted: 2025-01-09
• Study Start: 2025-03-01
• Primary Completion: 2026-03-01
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• 18 years of age or older
• Scheduled to undergo cadaveric liver transplant
• Meets at least one of the following criteria:
• Baseline fibrinogen <200 mg/dL
• Alcoholic cirrhosis
• Nonalcoholic Steatohepatitis (NASH)
• HCV infection

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Exclusion Criteria

• Living related donor transplant
• DCD liver recipient
• Known prothrombotic disorder
• Patient objection to blood transfusion
• Known severe allergic reaction to plasma-based products
• IgA deficiency with known hypersensitivity reaction to plasma
• Hepatocellular/cholangio carcinoma
• Primary biliary fibrosis

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Cryoprecipitate Antihemophilic Factor (AHF)	Cryoprecipitate Antihemophilic Factor (AHF)	AHF is the standard of care plasma product often used in liver transplant cases. The procedures to implementing AHF include requesting the order of this plasma product and then waiting for the product to be thawed for use, which can take approximately 10-15 minutes. Subjects assigned to this group will receive all standard of care procedures, including the use of AHF if required during their scheduled surgery.
Investigational Cryoprecipitate Intercept Fibrinogen Complex (IFC)	Cryoprecipitate Intercept Fibrinogen Complex (IFC)	IFC is an approved plasma product that is not typically stored in the OR for liver transplant cases. Subjects assigned to this group will receive standard of care procedures, with the addition of IFC being readily available in their designated OR to eliminate any delay if they are to require the use of a plasma product.

Primary Outcome Measures

Name	Time	Method
Amount of blood products (24-hours)	24-hours after initial blood product administration	The amount of blood products (mL) administered will be collected at the 24-hour timepoint per intervention group and reported as the mean (mL).

Secondary Outcome Measures

Name	Time	Method
Change in TEG parameters	14 days post-surgery	Change in TEG parameters, in particular the % change in the alpha angle will be calculated for each study participant and the effect size of the differences in the change, and 95% confidence interval.
Costs of blood products	14 days post-surgery	The costs (USD) of blood products used per intervention group will be collected 14-days post-surgery and reported as the mean (USD).
Costs of IV hemostatic agents	14 days post-surgery	The costs (USD) of IV hemostatic agents used per intervention group will be collected 14-days post-surgery and reported as the mean (USD).

Trial Locations

Locations (3)

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

UPMC Montefiore Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Presbyterian Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States