Blood-Bile Ratio Tacrolimus After Liver Transplantation (BBRT)

Use of Tacrolimus Blood-bile Ratio for the Detection of Early Liver Failure After Liver Transplantation

Tacrolimus is the most widely used immunosuppressive drug in the prevention of rejection after solid organ transplantation. Pharmacokinetic studies in healthy volunteers and in transplanted patients have shown that this molecule is rapidly absorbed after oral administration (maximum plasma concentration after 1-2 hours), is found in the circulation bound mainly to erythrocytes and, after being metabolized by CYP3A4, is eliminated through the bile. The importance of the tacrolimus blood dosage is now widely recognized for detecting the immunosuppressive capacity reached in the individual patient or the eventual overdose of the drug. In the use of Tacrolimus after Liver Transplantation, however, it is interesting to note that the biochemical pathway for metabolism and excretion of the drug is present in the transplanted organ, the main object of immunological and functional surveillance. The excretory capacity of Tacrolimus by the liver through the bile, therefore, could be a useful tool for recognizing the early liver failure from a functional point of view, before the onset of hepatoecrosis.

Study Overview

• Status: Unknown
• Conditions: Liver Transplant; Complications; Immunosuppression; Transplant; Complication, Rejection; Transplant Failure
• Intervention / Treatment: Diagnostic test: Blood-Bile Ratio of Tacrolimus

Detailed Description

Prospective monocentric randomized study comparing two parallel groups:

liver transplanted patients with early (10 POD) organ rejection (experimental arm); liver transplanted patients without early (10 POD) organ rejection (control arm) Primary Objective: Evaluation of a correlation between the reduction of Tacrolimus biliary excretion and the early liver failure Primary Endpoint: Increase of Tacrolimus blood-bile ratio measured before the onset of laboratory hepatonecrosis Secondary Objective: Analysis of the cause of any drug-related toxicity Secondary Endpoint: correlation study between drug dosage and biliary excretion level in case of blood overdose or clinical evidence of pharmacological toxicity

• Study Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• Italy
  • RM
    • Roma, RM, Italy, 00167
      • Marco Maria Pascale

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergone liver transplant with positioning of Kehr tube

Description

Inclusion Criteria:

• Age ≥18 years
• History of recent liver transplant (less than 10 days)
• Placement of kehr tube in the biliary tract during liver transplant
• Immunosuppressive therapy with Tacrolimus
• Functioning of kehr tube

Exclusion Criteria:

• Age - Age ≥18 years
• History of liver transplant for more than 10 days
• Liver transplant without positioning of kehr tube
• Immunosuppressive therapy with a drug different from Tacrolimus
• No functioning of kehr tube18 years
• History of liver transplant for more than 10 days
• Liver transplant without positioning of kehr tube
• Immunosuppressive therapy with a drug different from Tacrolimus
• No functioning of kehr tube

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rejection; Patient undergone liver transplant with diagnosis of rejection within 10 days	Diagnostic test: Blood-Bile Ratio of Tacrolimus; Diagnosis of early transplanted liver dysfunction to adjust Tacrolimus dose adminstered
No-Rejection; Patient undergone liver transplant wothout diagnosis of rejection within 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of early liver rejection	Evaluation of early liver rejection throught creation of a Tacrolimus blood-bile ratio	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of Tacrolimus toxicity	Evaluation of Tacrolimus toxicity throught blood dosage of the drug	10 days

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2019
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): May 1, 2020

Study Registration Dates

• First Submitted: March 17, 2019
• First Submitted That Met QC Criteria: March 17, 2019
• First Posted (Actual): March 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Liver transplant;; Immunosuppression;; Transplant rejection
• 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: PoliclinicoUAG-LTU

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes