Intervention to Improve Adherence in Teen Kidney Transplant

Study Overview
=================
Brief Summary
-----------------
The broad aim of the proposed study is to improve medication adherence in adolescent kidney transplant recipients. The investigators hypothesize that a multi-component intervention will improve medication adherence in the adolescent kidney transplant population. The specific aims are to determine, in a randomized clinical trial, the efficacy of a structured, multi-component intervention in improving adherence to anti-rejection medications and graft outcomes, and to identify characteristics of healthcare systems that are independently associated with adherence.

Detailed Description
-----------------
Young kidney transplant recipients at 8 pediatric transplant centers in the United States and Canada will be invited to participate. Participants will be randomly assigned to either the control or intervention group. Adherence will be measured in all participants using an electronic medication monitoring multi-dose pillbox. Enrolment will be followed by a 3-month run-in period, during which group allocation will be concealed and no intervention administered. At the 3-month visit, participants assigned to the intervention group will form an Adherence Support Team including the participant, one or both parents, and a study facilitator who is not a member of the treating team. At the same visit the facilitator will provide standardized adherence education, and will initiate a novel 20-30 min. behavioural intervention, which combines problem-solving skills with implementation intentions (concrete action plans in which an individual specifies, in an if-then contingency format, when, where and how he or she will perform a behaviour, with the goal of developing habits). This intervention will focus on addressing adherence barriers identified using the validated Medication Barriers Survey 3 and selected by the participant as important to him or her. Subsequent study visits, at 3-month intervals, will include a briefer versions of the educational component, and review and updating of implementation intentions. In addition, the electronic pillbox will be configured to provide alarm, phone, or text message dose reminders to participants in the intervention group throughout the intervention interval. Control participants will also meet with the facilitator at 3-month intervals, but will simply discuss general health and life issues; they will not receive dose reminders. In between visits, the facilitator will maintain monthly contact with all participants via short phone or text-message check-ins to troubleshoot issues with the electronic pillbox. The primary outcome will be 'taking adherence' - the proportion of prescribed doses that were consumed. Appropriate timing of doses will also be evaluated, as will variability in medication levels (reflecting consistency of medication consumption), and graft outcomes. Level of adherence, patterns of change in adherence, and graft outcomes will be compared between intervention and control groups. Secondary observational analyses of collected study data will identify healthcare systems factors independently associated with adherence.

Official Title
-----------------
TAKE-IT: Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial

Conditions
-----------------
Kidney Transplantation, Medication Adherence

Intervention / Treatment
-----------------
* Behavioral: Action-focused problem-solving
* Device: Electronic pillbox monitoring, dose reminders, and feedback


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects age 11 - 24 years At least 3 months post kidney transplant Exclusion Criteria: Significant neurocognitive disabilities limiting the subject's ability to understand and participate on their own Unable to communicate in English or French (Montreal site) Unable to communicate in English (all other sites)

Ages Eligible for Study
-----------------
Minimum Age: 11 Years
Maximum Age: 24 Years

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

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

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

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multi-component Intervention<br>Multi-component Intervention consisting of: Adherence Support Team (patient, parent, Coach) standardized education on immunosuppressive medications identification of adherence barriers Electronic adherence monitoring with feedback of past 3 months of electronic monitoring data at 3-month intervals 'Action-Focused Problem-Solving' to address barriers selected as most important by the patient text message, email, or visual cue dose reminders | Behavioral: Action-focused problem-solving<br>* Adherence Support Team (patient, parent, Coach) standardized education on immunosuppressive medications identification of adherence barriers 'Action-Focused Problem-Solving' to address barriers selected as most important by the patient<br>Device: Electronic pillbox monitoring, dose reminders, and feedback<br>* Electronic adherence monitoring with feedback of past 3 months of electronic monitoring data at 3-month intervals text message, email, or visual cue dose reminders<br>* Other names: SimpleMed medication reminder and dispenser;|
| No Intervention: Attention control<br>Control group study visits were conducted at the same intervals as intervention visits and consisted of the Coach engaging in active listening and providing non-specific support only. Adherence was NOT discussed with control participants. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Taking Adherence | Daily taking adherence, defined as the percentage of prescribed doses taken each day (as measured by electronic monitoring). The daily taking adherence score could take a value of 0%, 50%, or 100% for patients on twice daily dosing, and 0% or 100% for patients on once daily dosing. Each patient had a taking adherence score for every day of observation (repeated measures). On days that the pillbox was not in use due to technical problems or participant non-use (due to travel etc), no score was given. To summarize adherence for each arm, we calculated the total percentage of days of observation for which there was 100% taking adherence. The denominator for this calculation was the the total number of days of observation of each participant, summed across all participants; the numerator was the total number of days of observation of each participant for which taking adherence was 100%, summed across all participants. | 12 months | 
| Timing Adherence | Daily timing adherence, defined as the percentage of doses taken within 1 hour before to 2 hours after the prescribed dosing time each day (as measured by electronic monitoring). The daily timing adherence score could take a value of 0%, 50%, or 100% for patients on twice daily dosing, and 0% or 100% for patients on once daily dosing. Each patient had a timing adherence score for every day of observation (repeated measures). On days that the pillbox was not in use due to technical problems or participant non-use (due to travel etc), no score was given. To summarize timing adherence for each arm, we calculated the total percentage of days of observation for which there was 100% timing adherence. The denominator for this calculation was the the total number of days of observation of each participant, summed across all participants; the numerator was the total number of days of observation of each participant for which timing adherence was 100%, summed across all participants. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standard Deviation (SD) of Tacrolimus Trough Levels | The SD of all tacrolimus trough levels done for clinical care (except during hospitalizations or illnesses) were calculated for participants with >=3 tacrolimus levels. | 12 months | 
| Self-reported Taking Adherence | Self-reported taking adherence, assessed using the Medical Adherence Measure- Medication Module (MAM-MM), was scored as the proportion of doses taken in the previous week. MAM-MM scores for each patient were summarized as the mean of the four scores post-intervention. | 12 months | 
| Self-reported Timing Adherence | Self-reported timing adherence, assessed using the Medical Adherence Measure- Medication Module (MAM-MM), was scored as the proportion of doses taken up to 2 hours after the prescribed time in the previous week. MAM-MM scores for each patient were summarized as the mean of the four scores post-intervention. | 12 months | 
| Acute Rejection Rate | The acute rejection rate, measured as rejections per 100 person-years of observation. | 12 months | 
| Annualized Change in Estimated Glomerular Filtration Rate (eGFR) | Change in estimated glomerular filtration rate, estimated using the Schwartz equation for those < 18 y. and the CKD-EPI equation for those 18y and older, standardized to a 12-month period. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
renal, allograft, immunosuppressive, immunosuppression, adherence, medication, compliance