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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Transplant
• Intervention / Treatment: Drug: Tacrolimus Sustained-release Capsules

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hao Feng, MD., Ph.D; Phone Number: 008615000901110; Email: surgeonfeng@live.com

Study Locations

• China
  • Shanghai, China
    • Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
    • Contact: Hao Feng; Phone Number: +8615000901110; Email: surgeonfeng@live.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Children (≤18 years old) who have undergone liver transplantation, with no gender limitations;
2. Able to completely swallow capsules;
3. Have been using immediate-release tacrolimus for at least three months prior to study enrollment;
4. Have normal blood count, liver and kidney function, coagulation function, and considered clinically stable by researchers;
5. Undergo a programmed liver biopsy;

Exclusion Criteria:

1. Multi-organ combined transplantation or multiple liver transplantation;
2. Adjuvant liver transplantation or use of bioartificial liver therapy;
3. ABO incompatible children with liver transplantation;
4. Allergic to tacrolimus;
5. Participation in any other clinical study within 3 months prior to enrollment;
6. Use of tacrolimus sustained release capsules before enrollment;
7. Tacrolimus trough concentration lower than 3.5 ng/ml at the time of screening;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolonged-release tacrolimus	Drug: Tacrolimus Sustained-release Capsules; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Study Chair: Qiang Xia, Prof. MD, Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU; Principal Investigator: Hao Feng, MD., Ph.D, Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: December 27, 2023
• First Posted (Actual): December 28, 2023

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: liver transplant; pediatric liver transplant; tacrolimus
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: Renji-LY2023-076-B

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