Transplant Regimen Adherence for Kidney Recipients by Engaging Information Technologies: The TAKE IT Trial

Study Overview
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Brief Summary
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The investigators will evaluate a technology-enabled strategy designed to promote medication adherence, routinely monitor regimen use, and mobilize appropriate transplant center resources to respond early to kidney transplant recipients demonstrating inadequate adherence.

Detailed Description
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The investigators will evaluate a technology-enabled strategy designed to promote medication adherence, routinely monitor regimen use, and mobilize appropriate transplant center resources to respond early to kidney transplant recipients demonstrating inadequate adherence. Among patients receiving a kidney transplant (KT), the 5-year risk of organ (graft) failure is high; 30% for deceased donor and 27% for living donor recipients. Medication non-adherence is a leading root cause of graft failure, and KT recipients have the highest reported rate of poor adherence ( 35%) among all organ transplant recipients. Despite many attempts, there have been few successful interventions evaluated to date that have significantly improved KT recipients' regimen adherence and subsequent health outcomes over time. There are many reasons why individuals may not take medication regimens as prescribed, including but not limited to: forgetfulness, misunderstanding, regimen complexity, side effects, health issues, social support, motivation and cost. Therefore no single solution can address all patients. A healthcare team must understand the precise nature of a patient's adherence barriers in order to properly respond. Yet medication adherence is not clinically assessed as part of routine post-transplant care, and prior studies have found that medical staff cannot readily identify poor adherence among patients, let alone the reasons why. Using evidence from the research team's extensive previous studies in other chronic disease contexts, the investigators will implement and comprehensively test a potentially low cost, 'low touch', thus highly scalable intervention: the Transplant regimen Adherence for Kidney recipients by Engaging Information Technologies (TAKE IT) strategy. The TAKE IT strategy leverages a transplant center's electronic health record and a web-based patient portal, as well as mobile technology to: 1) educate patients on their prescribed Rx regimens, 2) help them organize their daily regimen schedule in the most efficient manner, 3) remind them via SMS (Short Message Service) text when to take their medicine, 4) routinely monitor regimen use, and 5) provide care alerts to engage appropriate transplant center clinical staff (e.g. nurse coordinator, pharmacist, social worker) when medication concerns are detected. All components of the TAKE IT strategy have been developed with prior NIH support, refined with 'user' input (patient, family, clinic staff), and their efficacy tested in non-transplant settings. The research team's primary aim and hypotheses (H) are to: Aim 1 Test the effectiveness of the TAKE IT strategy, compared to usual care, to improve KT recipients': H1 treatment knowledge (indications, potential side effects, demonstrated proper use) H2 medication use (regimen adherence via self-report, pill count, pharmacy records, tacrolimus levels) H3 transplant-specific outcomes (Δ eGFR (estimated glomerular filtration rate), quality of life, re-hospitalization) H4 chronic disease outcomes (blood pressure, HbA1c) They will conduct a 2-arm, patient-randomized controlled trial at two large, diverse transplant centers (Northwestern University; Mayo Clinic). 300 KT recipients within 3 months of transplant ('de novo') and 400 'established' patients between 18 months and 3 years post-KT will be recruited and followed for 2 years (N=700 patients; n=350 per site and n=175 per study arm within each site). In-person interviews will be conducted at baseline, 6, 12, 18 and 24 months. To determine proximal effects of the TAKE IT strategy, a telephone interview will also be administered 6 weeks post-baseline. Electronic health and pharmacy records will be ascertained to capture medication adherence and clinical outcomes. The secondary aims are to: Aim 2 Examine the persistence of any effects of the TAKE IT strategy on outcomes over 2 years among new and established KT recipients. Aim 3 Evaluate the fidelity of each component of the TAKE IT strategy over time, and investigate any patient, provider, or transplant center barriers to implementation. Aim 4 Determine the costs of delivering the TAKE IT strategy from a transplant center perspective. Additionally, the investigators will closely evaluate the implementation of all components of the TAKE IT strategy from launch through 2 years follow-up (Aim 2). Their evaluation will include a range of process outcomes to assess the intervention's reliability and sustainability. These findings will determine whether any specific modifications to the TAKE IT strategy are necessary (Aim 3). Finally, the team will estimate the incremental costs of implementing and sustaining the TAKE IT strategy from the perspective of two transplant centers (Aim 4).

Official Title
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Transplant Regimen Adherence for Kidney Recipients by Engaging Information Technologies: The TAKE IT Trial

Conditions
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Kidney Transplant

Intervention / Treatment
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* Behavioral: TAKE IT Strategy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) age 21 or older 2) 5 weeks to 24 months post kidney transplant 3) English speaking 4) primarily responsible for administering own medication 5) owns a cell phone and comfortable receiving text messages 6) has access to and proficiency using internet in home Exclusion Criteria: any severe, uncorrectable vision, hearing or cognitive impairments

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to one of two arms: TAKE IT strategy or usual care.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual Care<br>Patients in this group will receive the usual standard of care. | |
| Experimental: Intervention<br>Patients in this group will receive the TAKE IT strategy components. | Behavioral: TAKE IT Strategy<br>* The TAKE IT Strategy includes: Programming the electronic health record (EHR) to organize/simplify daily regimen schedules and generate electronic, tangible, print, low literacy medication education materials at every clinical encounter. SMS text-messaging to remind patients when to take all their medicine. A web-based patient portal that requests patients to periodically report upon their medication use, providing a continuous link between the transplant center and patient beyond routine in-person visits. EHR notifications directed to the transplant center nurse coordinator if an adherence-related problem is identified by the web-based portal assessment, who then can activate appropriate staff to respond.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rx pill count | An in-person pill count using established guidelines will be conducted. When in-person interviews are not possible, pill count will be done over the phone. Adherence will be assessed within drugs. The proportion of pills taken/pills prescribed will be calculated per medication. Patients will be considered non-adherent for a medication if this score is <=80%. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 hour recall | Patient self-report of how many pills and how often each medicine was taken over the last 24 hours. Correct dosing will be measured as yes/no per drug, having properly shown dose (# pills), spacing (hours between doses), frequency (times per day), and total pills/day. | 1 year | 
| Ask-12 | The Ask-12 is a self-report scale that assesses general medication attitudes and beliefs. The scale consists of 12 items across three domains (inconvenience/forgetfulness, treatment beliefs, and behaviors), with responses ranging from Strongly Disagree to Strongly Agree. Score can range from 12-60 with higher scores representing greater barriers to adherence. | 1 year | 
| Change in eGFR (estimated glomerular filtration rate), ml/mm | Change in eGFR rate over 2 years | 2 years | 
| Re-hospitalization | Acute care hospitalizations post transplant | 2 years |