Medication Adherence in Children Who Had a Liver Transplant (MALT)

The purpose of this study is to evaluate the use of a novel method to measure adherence to immunosuppressant medications in predicting rejection episodes in children who had a liver transplant.

Study Overview

• Status: Completed
• Conditions: Pediatric Recipients of a Liver Transplant

Detailed Description

During the course of their illness as many as 50% of children who had a liver transplant stop taking their medications. Non-adherence is the most important reason for organ rejection in long term survivors of pediatric liver transplantation. In order to address this important risk-factor effectively, the first step is to evaluate a method that would identify non-adherence in these children. Medication blood levels that are obtained as a part of clinical practice in transplant centers can be used to determine whether the patient is adherent or not. This multi-center observational study tests the ability of an objective measure of adherence to immunosuppressant medications that involves the use of routinely obtained tacrolimus blood levels to predict organ rejection in children who had a liver transplant.

• Study Type: Observational
• Enrollment (Actual): 401

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital
  • New York
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients receiving liver transplantation

Description

Inclusion Criteria:

• The patient is between > 1 year of age and less than 18 years of age at enrollment
• Guardian's consent, child assent (in accordance with each institution's IRB policies).
• The patient is prescribed tacrolimus (either brand or generic formulation).
• The patient has been seen in the enrolling center's clinic at least once in the last two years.

Exclusion Criteria:

• The patient received a liver transplant less than 1 year prior to enrollment.
• The patient has had more than one solid organ transplant (including marrow replacement).
• The patient has had biopsy-proven rejection within the past six months.
• The patient has been diagnosed with Hepatitis C.
• The guardian or child (in a developmentally-appropriate manner) do not understand the study procedures. This will be verified by asking both guardian and child (if 6 years old or older) to repeat the study procedures.
• The patient is only seen for consultation - most or all of the child's routine care is provided at another center (or in a community clinic).
• Either the patient or the guardian is actively psychotic or severely disoriented due to any cause, including hepatic encephalopathy (temporary exclusion) or severely mentally retarded as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).
• The patient is not medically stable or is hospitalized.
• The treating physician has instructed the participant not to obtain tacrolimus levels for at least one year.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rejection episodes	Adherence measured through the use of the standard deviation of a series of tacrolimus blood levels obtained during the course of follow-up is the primary predictor.	Quarterly for 2 years unless a rejection occurs within this time frame.

Secondary Outcome Measures

Outcome Measure	Time Frame
Retransplantation or death	2 years
Liver function tests	Quarterly for 2 years unless a rejection occurs within this time frame.

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of California, Los Angeles; University of Pittsburgh; Ann & Robert H Lurie Children's Hospital of Chicago; Children's Hospital Medical Center, Cincinnati; The Emmes Company, LLC

Publications and helpful links

General Publications

• Shemesh E, Bucuvalas JC, Anand R, Mazariegos GV, Alonso EM, Venick RS, Reyes-Mugica M, Annunziato RA, Shneider BL. The Medication Level Variability Index (MLVI) Predicts Poor Liver Transplant Outcomes: A Prospective Multi-Site Study. Am J Transplant. 2017 Oct;17(10):2668-2678. doi: 10.1111/ajt.14276. Epub 2017 Apr 22.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: June 29, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (ESTIMATE): June 30, 2010

Study Record Updates

• Last Update Posted (ACTUAL): December 26, 2017
• Last Update Submitted That Met QC Criteria: December 21, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Adherence; Tacrolimus; Compliance; Liver transplant
• Other Study ID Numbers: GCO 09-1112; R01DK080740 (NIH)