Antithrombin III Concentrate After Liver Transplantation

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

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.

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

Conditions
-----------------
Liver Transplant; Complications

Intervention / Treatment
-----------------
* Drug: Antithrombin III, continuous infusion
* Drug: Antithrombin III, Intermittent infusion


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous infusion<br>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<br>* Antithrombin-III is administered continuously<br>* Other names: Antithrombin III, human;|
| Active Comparator: Intermittent infusion<br>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<br>* Antithrombin-III is administered intermittently<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
antithrombin III, liver transplantation, administration method, dosage