Antithrombin III Concentrate After Liver Transplantation

Continuous Versus Intermittent Infusion of Human Antithrombin III Concentrate in the Immediate Postoperative Period After Liver Transplantation

This study was designed to demonstrate more effective administration method of AT-III in immediate post-liver transplantation period.

Study Overview

• Status: Completed
• Conditions: Liver Transplant; Complications
• Intervention / Treatment: Drug: Antithrombin III, continuous infusion; Drug: Antithrombin III, Intermittent infusion

Detailed Description

Antithrombin III(AT-III) concentrates have been used to prevent critical thrombosis in the immediate post-liver transplantation period without clear evidence regarding the optimal dose or administration scheme.

The investigators retrospectively analyzed the clinical data from the patients who received liver transplantation and developed pharmacokinetic model of AT-III in the previous research. According to this study, optimal AT-III activity level will be well-maintained with smaller dose with continuous infusion than with intermittent infusion which is widely accepted way of administration currently.

A prospective study was planned to show the more effective manner of AT-III concentrate administration after liver transplantation.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University 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:

• Scheduled operation
• Living donor liver transplantation
• Adult patients (>=18 years old)

Exclusion Criteria:

• Patients under 18 years old
• Emergency operation
• Deceased donor liver transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous infusion; Immediately after operation, 2000 international unit (IU) of Antithrombin-III (AT-III) concentrate is loaded for 1 hour. AT-III concentrate 3000 IU is continuously infused through following 71 hours.	Drug: Antithrombin III, continuous infusion; Antithrombin-III is administered continuously; Other Names: Antithrombin III, human
Active Comparator: Intermittent infusion; Every 6 hours, 500 IU of AT-III concentrate is infused through 1 hour during the first 72 hours after liver transplantation.	Drug: Antithrombin III, Intermittent infusion; Antithrombin-III is administered intermittently; Other Names: Antithrombin III, human

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients within target range at postoperative 72 hours	Proportion of patients whose AT-III activity level is within the target range (80-120%)	72 hours after liver transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients within target range at postoperative 12/24/48/84 hours	Proportion of patients whose AT-III activity level is within the target range (80-120%)	12/24/48/84 hours after liver transplantation
Proportion of AT-III level values within target range	Among the measured AT-III activity levels, proportion of the values within the target range (80-120%)	12/24/48/72/84 hours after liver transplantation
Time required for AT-III level value to fall within target range	Time required for AT-III level value to fall within target range (80-120%, hours)	operation day ~ postoperative day 7
Duration for cessation of AT-III concentrate administration	AT-III infusion is stopped for 24 hours when AT-III plasma activity level exceeds 120%, then restarted after the value is confirmed to be less than 120%.	operation day ~ postoperative day 7
Bleeding requiring intervention	Bleeding requiring intervention	operation day ~ postoperative day 7
Thrombosis event	Hepatic artery thrombosis, portal vein thrombosis	operation day ~ postoperative day 7
Postoperative hospital stay	number of days from operation to discharge	through the hospital day, an average of 14 days

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Study Chair: Ho Geol Ryu, MD, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2020
• Primary Completion (Actual): June 28, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: December 29, 2019
• First Submitted That Met QC Criteria: January 5, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: liver transplantation; antithrombin III; administration method; dosage
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Anticoagulants; Antithrombins; Antithrombin III
• Other Study ID Numbers: HGRyu_AT-III

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