Technology Enabled Strategies to Promote Treatment Adherence in Liver Transplant

Study Overview
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Brief Summary
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Liver transplantation is increasingly performed for older adults with multiple comorbidities. Medication adherence is key to maintaining proper function of the transplanted liver and optimize health; however, adhering to post-transplant treatment is complex. This trial will study how available technology combined with transplant center resources and caregiver support can optimize medication adherence, quality of life, and health outcomes among new liver transplant recipients at 3 centers.

Detailed Description
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Liver transplant, the only cure for end-stage liver disease, is a costly and limited resource that increases survival. It is increasingly performed among older adults who have a higher burden of comorbidities, medical complexity, and are at risk of non-adherence. In addition, liver transplant recipients must manage complex immunosuppression regimens to maintain graft function. Inadequate immunosuppression adherence is common post-liver transplant and has many adverse consequences including liver graft rejection, graft failure, and re-transplantation. To maintain their health, liver transplant recipients must also self-manage regimens for multiple chronic conditions beyond liver transplant. The TEST Trial intervention is a conceptual framework to address health system and patient level barriers to adherence. By following the Cumulative Complexity Model and the Multiple Chronic Conditions Model, this study focuses on liver transplant recipients and their involved caregivers. The TEST trial leverages the use of electronic health record and Way to Health (W2H) text message system to improve medication adherence. TEST is a 2-arm, patient-randomized controlled trial at three large, diverse transplant centers: University of Pennsylvania (UPENN), Northwestern University (NU); University of Miami (UM). A total of 360 de novo LTRs age 50 or older (n=180 per arm) within 3 months of transplant will be recruited and randomized to intervention versus usual care for 18 months. Interviews will be conducted at baseline, 6, 12, and 18 months. The TEST intervention includes: Monthly W2H Adherence Assessment & Clinician Alerts Medication Reminders Laboratory and Appointment Notifications Supplemental Self-Management Support The primary objective of the study is to investigate the effectiveness of the TEST Trial to improve adherence to immunosuppressant and non-immunosuppressant medication regimens, functional health status, and health outcomes compared to usual care. Secondary objectives will measure study fidelity and cost effectiveness.

Official Title
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Technology Enabled Strategies to Promote Treatment Adherence in Liver Transplant

Conditions
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Liver Transplant; Complications, Cirrhosis, End Stage Liver DIsease, Medication Adherence

Intervention / Treatment
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* Behavioral: TEST Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver Transplant recipients who are: 18 years or older Within 3 months of liver transplant English or Spanish-speaking Home-dwelling Patient or caregiver owns a cell phone and is comfortable receiving text messages and/or using internet in home. Exclusion Criteria: Any severe uncorrectable vision, hearing, or cognitive impairments that may impede study interviews

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: This is a longitudinal intervention study utilizing diverse cohorts of liver transplant recipients. It is a 2-arm, patient-randomized controlled trial of de novo liver transplant recipients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual Care<br>Usual care refers to the normal standard clinical practices immediately post-transplant to the 18 months following. Liver Transplant Recipients at sites have lab values taken weekly for the first 8-10 weeks post-transplant, shifting to every 2-4 weeks for the next 3-4 months, then monthly to every 3 months thereafter depending on clinical needs. All sites follow a similar schedule of tapering clinic visits ranging from weekly in the first 4 weeks to every 2-4 weeks in months 4-6, every 3-6 months in months 7 12, and every 6 months in months 12-24. All sites assign each patient to a specific transplant coordinator, first paired with a transplant surgeon (first 3-6 months), and then a transplant hepatologist for the remainder of follow-up. All patients and caregivers receive standard medication teaching prior to hospital discharge and then ad hoc. No routine text message reminders, caregiver reminders, or adherence alerts are used in usual care. | |
| Experimental: TEST Intervention<br>Clinical activities for Usual Care will also be provided in the TEST arm. The TEST intervention is a technology-enabled strategy to routinely monitor regimen use, adherence, and persistence via a 'low touch', easy to use, online behavioral toolkit - Way to Health . It was developed by University of Pennsylvania researchers to automate behavioral intervention. The TEST approach includes monthly adherence assessments, with tailored adherence support. The following components will be included in the intervention: Monthly W2H Adherence Assessment & Clinician Alerts Medication Reminders Laboratory and Appointment Notifications Supplemental Self-Management Support | Behavioral: TEST Intervention<br>* The TEST intervention will include standard post-transplant care and include additional touchpoints utilizing the Way to Health system. Details on this intervention are included in the study arm description.<br>|

What is the study measuring?
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Primary 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. Patients will also be asked about the medical indication for each drug. Correct dosing will be measured as a yes/no per drug, having properly shown dose (number of pills), spacing (hours between doses), frequency (times per day), and total pills/day. | 18 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tacrolimus Lab Values, ng/mL | Tacrolimus lab values (ng/mL) will be tracked. Patient immunosuppression variability will be assessed with the tacrolimus coefficient of variation (COV) (100 x standard deviation/mean tacrolimus concentration) and the medication level variability index (MLVI, standard deviation of at least three values. The range for COV is 0-1 , and the MLVI range generally falls between 0-9. Nonadherence to medication can be seen in values >= 0.30 for COV and greater than 2.5-2.6 for MLVI. Fidelity will be measured through the number of completed monthly assessments, patient/caregiver engagement with text messages, and percent care alerts with clinical actions taken. | 18 Months | 
| ASK-12 | The ASK-12 is a self-report scale that assess general medication attitudes and beliefs. The scale consists of 12 items across three domains (inconvenience/forgetfulness, treatment beliefs, and behaviors), with responses ranging from Strong Disagree to Strongly Agree. The score can range from 12-60 with higher scores representing greater barriers to adherence. | 18 Months | 
| EQ-5D-5L | Patient health outcomes will be measured using the EQ-5D-5L questionnaire. This tool measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and self-rated health. Each dimension has 5 levels: no problem, sight problems, moderate problems, severe problems, and extreme problems. Patient choice for each results in a 1-digit number that expresses the level selected, and the digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. A lower score indicates a good health state while a higher score represents a more severe health state. In addition, there is a visual analogue scale (VAS) to indicate the general health status with 100 indicating the best health status and 0 being the worst health state | 18 Months | 
| 30-Second Chair Stand | The 30-Second Chair Stand test is a measure of leg strength and endurance. The patient is asked to move from a seated position with arms crossed over the into the standing position and then sit back down. The test administrator counts the number of times the patient comes to a full standing position in 30 seconds. The number of successful completions indicates the risk of fall. This score is dependent on age category with <14 for men and <12 for women between the age of 60-64 indicating a greater risk for all | 18 Months | 
| Timed Up and Go Test (TUG) | The Timed up and Go Test (TUG) assess patient mobility. Patients begin by sitting in a chair and identify a line or object 10 feet away they can walk to. The administrator measures how long it takes (sec) for the patient to stand up, walk the 10 feet in a straight line, and sit back down. Patients should walk at their normal pace. The administrator makes not of any issues with the patient's postural stability, gait, stride length, and sway. The changes may signify neurological problems. An older adult who takes >= 12 seconds to complete the TUG is at risk for falling | 18 Months | 
| Days Alive Out of Hospital | The number of days a patient spends alive and not hospitalized for any reason | 18 Months | 
| Liver Graft Outcomes | The number of instances of liver graft rejection and liver graft failure post-transplant | 18 Months | 
| Post-Transplant Infection | The number of instances of patient having an infection (bacterial, viral, or fungal) post-transplant | 18 Months | 
| Mortality | If a patient passes away in the study, the date of death and cause of death will be recorded along with the number of days death occurred post-transplant | 18 Months |