Prospective, Multicenter Clinical Study of Prolonged-release Tacrolimus in Stable Pediatric Liver Transplant Recipients

Study Overview
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Brief Summary
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This study aims to explore the effects of tacrolimus sustained-release capsules on the incidence of biopsy-proven acute rejection(BPAR) and fibrosis in pediatric liver transplant recipients.

Detailed Description
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Tacrolimus is a commonly used immunosuppressant after liver transplantation. However, with increased postoperative time and a decline in postoperative compliance, some children may miss medication, leading to acute rejection. Repeated rejection can cause fibrosis of the transplanted liver, seriously impacting graft function and even postoperative survival, sometimes resulting in the need for a second liver transplant. In adult liver transplant recipients, tacrolimus sustained-release capsules have been shown to significantly improve overall and transplanted liver survival compared to conventional formulations (immediate-release tacrolimus，taken twice daily). Therefore, this study aims to explore the effects of tacrolimus sustained-release capsules on the incidence of biopsy-proven acute rejection(BPAR) and fibrosis in pediatric liver transplant recipients.

Official Title
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Prospective, Multicenter Clinical Study of Prolonged-release Tacrolimus in Stable Pediatric Liver Transplant Recipients

Conditions
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Liver Transplant

Intervention / Treatment
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* Drug: Tacrolimus Sustained-release Capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children (≤18 years old) who have undergone liver transplantation, with no gender limitations; Able to completely swallow capsules; Have been using immediate-release tacrolimus for at least three months prior to study enrollment; Have normal blood count, liver and kidney function, coagulation function, and considered clinically stable by researchers; Undergo a programmed liver biopsy; Exclusion Criteria: Multi-organ combined transplantation or multiple liver transplantation; Adjuvant liver transplantation or use of bioartificial liver therapy; ABO incompatible children with liver transplantation; Allergic to tacrolimus; Participation in any other clinical study within 3 months prior to enrollment; Use of tacrolimus sustained release capsules before enrollment; Tacrolimus trough concentration lower than 3.5 ng/ml at the time of screening;

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolonged-release tacrolimus<br> | Drug: Tacrolimus Sustained-release Capsules<br>* Immediate-release tacrolimus for at least 3 months after liver transplantation, and then convert to tacrolimus sustained-release capsules at a ratio of 1:1 to 1:1.2; Take the medicine once a day on an empty stomach in the morning. (The specific medication plan is decided by the clinician according to the actual situation)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of biopsy-confirmed acute rejection (BPAR) | biopsy-confirmed acute rejection (BPAR) would be evaluated by the international Banff classification | 12 months | 
| Incidence of allograft liver fibrosis | allograft liver fibrosis would be evaluated by LAFSc | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver function | alanine transaminase (ALT) and aspartate transaminase (AST), serum bilirubin, prothrombin time (PT), and albumin within and 12 months after conversion | 12 months | 
| Kidney function | creatinine (Cr) and BUN within and 12 months after conversion | 12 months | 
| Liver allograft survival rate | Liver allograft survival rate at 12 months after conversion | 12 months | 
| The rate of drug change | The rate of drug change caused by ultrasonic diagnosis and abnormal liver function index suspected AR (from tacrolimus sustained release to other CNI drugs) | 12 months | 
| Incidence of infection | Incidence of infection (viral, bacterial and fungal) at 12 months after conversion | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver transplant; pediatric liver transplant; tacrolimus