Improving Medication Adherence in Adolescents Who Had a Liver Transplant

Study Overview
=================
Brief Summary
-----------------
The study's aim is to test a tailored telemetric intervention to reduce rejection incidence by improving medication adherence in a group of adolescent liver transplant recipients identified as nonadherent by a marker (the Medication Level Variability Index, MLVI).

Detailed Description
-----------------
This is a prospective, multi-center, randomized controlled trial. The study will be conducted in transplant centers in the United States and Canada. Estimated final sample size of 140 after attrition. Pediatric adolescent and young adult (age at enrollment ≥12 and < 20) transplant recipients will be eligible for participation in the study. Eligible participants will be randomly assigned to intervention or control group. An interim analysis to evaluate efficacy will be performed. Missing data will not be imputed for secondary analyses.

Official Title
-----------------
Improving Medication Adherence in Adolescents Who Had a Liver Transplant

Conditions
-----------------
Transplant

Intervention / Treatment
-----------------
* Behavioral: Telemetric Intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patient is ≥ 12 and < 20 years of age at enrollment. ≥2.5 years after last liver transplantation. Guardian's consent, adolescent assent at enrollment. The patient is prescribed tacrolimus. The patient's MLVI (SD of tacrolimus) was > 2 when calculated by the site for a period of 2 years prior to the review date Exclusion Criteria: The patient has had transplant of an organ other than liver. The patient is currently listed for any organ transplantation. The patient is expected to transition to another service (e.g., adult clinic, another hospital) during the two years of the study. Pregnant patients. A temporary exclusion: the patient is not medically stable or was hospitalized for >48 consecutive hours in the past three months. Site PI, study PI, or Medical Monitor determines that the patient should not be a candidate for the intervention due to factors that are not covered in the above criteria.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 19 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study participants will be randomized to receive the telemetric intervention or standard of care.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telemetric Intervention Arm<br>Adolescent with MLVI>2 to receive the telemetric intervention. | Behavioral: Telemetric Intervention<br>* Calls, scripted by a manual; the frequency of the calls varies with patient's MLVI status and preferences.<br>|
| No Intervention: Standard of Care Arm<br>Adolescent with MLVI>2 to receive standard of care. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Rejection | The incidence of biopsy-proven acute cellular rejection (number of patients experiencing at least one episode of rejection) at any time during the 2 years of follow up.Biopsy-confirmed late acute rejection, as determined by the majority of 3 masked readings of liver biopsy images by 3 pathologists that are not from the clinical site at which the patient is treated. Patients with incomplete follow-up (for example due to death, re-transplant, listing for re-transplantation), will be assumed to have experienced a rejection for the purpose of the primary analysis. | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Standard Deviation of A Series Of Tacrolimus Levels (MLVI) | MLVI = Standard Deviation Of Tacrolimus Blood Levels | 2 Years | 
| Incidence of Locally Determined Biopsy Proven Rejection |  | 2 Years | 
| Rate Of Locally Determined Biopsy Proven Rejection |  | 2 Years | 
| Rate of Centrally Determined Biopsy Proven Rejection |  | 2 Years | 
| Time to Rejection From Enrollment |  | 2 Years | 
| Occurrence of Death | Number of deaths | 2 Years | 
| Occurrence of Re-Listing For Transplantation | Number of participants listing for retransplantation | 2 Years | 
| Mean ALT | Mean number of achieving above threshold ALT > 150 Alanine Aminotransferase (ALT) | 2 Years | 
| Mean maximal ALT | mean/maximal and ALT (defined as in MALT as the mean of all levels recorded during the study period and the maximal level recorded during the study period) | 2 Years | 
| Mean gGT | Mean number of achieving above threshold GGT > 150 Gamma Glutamyl Transferase (gGT) | 2 Years | 
| Mean maximal gGT | mean/maximal gGT (defined as in MALT as the mean of all levels recorded during the study period and the maximal level recorded during the study period) | 2 Years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adherence, Intervention