Improving Adherence in Nonadherent Kidney Transplant Patients

Study Overview
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Brief Summary
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Organs for transplantation remain a scarce and precious resource with over 5000 patients currently on the kidney transplant waiting list. A kidney transplant costs approximately £17,000 in the first year and £5,000 per subsequent year. If the transplant fails, the patient must return to dialysis at an estimated cost of £30,800 per year or be retransplanted. While short term outcomes have improved steadily over the last 15-20 years, longer term outcomes haven't and after 10 years approximately 30% of kidney transplants have failed. Nonadherence to immunosuppressive medication is increasingly being associated with these poor long term outcomes and studies have estimated that 30- 50% of transplant patients are nonadherent to their immunosuppressive medication. The investigators want to determine whether immunosuppression medication adherence can be improved in a group of patients receiving tailored medication adherence support form a pharmacist. Adherence support will be provided for one year and will be individualised to each patient in the intervention group after identifying both their practical and perceptual barriers to adherence. The adherence interventions offered may include additional education and medication counselling, setting alarms, provision of a medication list, the use of a medications adherence app on a smart phone, reducing the number and frequency of tablets a patient takes or referral on to another health professional such as a social worker or psychologist for additional support. A range of clinical outcomes will be assessed for all patients on a regular basis in order to determine whether the provision of effective medication adherence support for our kidney transplant patients may help to optimise the long-term outcomes of these transplants

Detailed Description
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This study will be undertaken using a prospective, multidimensional design. 42 nonadherent kidney transplant patients will be included in the intervention group. The nonadherent patients will be identified through Imperial College Renal and Transplant Centre (ICRTC) Outpatient Clinic based at Hammersmith Hospital. Standard and transplant specific demographics will be collected for all patients. All kidney transplant patients have their tacrolimus levels measured at each clinic visit. The variability of these levels can be used as a marker of their adherence. Patients with a high intrapatient variability (IPV) of their levels are said to be nonadherent. The Chief Investigator or another member of the research team will approach individual patients directly in the transplant out-patient clinic where they are members of the multidisciplinary clinical care team. The Chief Investigator or another member of the research team may also telephone patients to invite them to clinic to discuss participation in the trial. The Chief Investigator or another member of the research team will describe the study to the patient, answer any questions they have and provide them with a participant information sheet (PIS). Patients will be given the opportunity to take the PIS away and think about whether they would like to participate. A follow up discussion either in clinic or on the phone will be arranged with the patient to answer any queries they have within two weeks of providing them with the PIS; during that discussion, the Chief Investigator or other member of the research team will arrange an appointment in the transplant clinic with the patient to sign the consent form if they do decide to participate. Patients recruited into the study will receive pharmacist led, patient tailored interventions to improve immunosuppressant medication adherence. Patients will be included in the study for one year from recruitment. The pharmacist led, patient tailored intervention will involve regular, intensive, personalised support from a pharmacist to improve adherence to immunosuppressive medications. The pharmacist will meet with the patient on a regular basis in the transplant clinic to identify their perceptual and practical barriers to adherence and agree a support plan that is tailored to them. Within the first two weeks of recruitment, the study pharmacist will meet with the patient in transplant clinic to: Undertake a full medication history Discuss self-reported medication nonadherence Undertake the BAASIS questionnaire Ask the patient to complete a Beliefs about Medicines Questionnaire (BMQ) Undertake a socioeconomic and educational assessment Undertake to gain collateral reporting of nonadherence by clinicians, relatives, friends or carers Perform a tacrolimus pill count Check in-house dispensing records of tacrolimus Identify barriers to adherence Tailor interventions and support to the needs of the patient Complete a motivational interview Agree to meet again during an outpatient clinic visit within an agreed time which is appropriate for the patient needs and within 3 months. This first visit will provide a baseline assessment of the patient's medication adherence. Tailored support may include: Setting alarms Medication diary card or calendar Medication compliance aid filled by the patient, family/carers or by a pharmacy professional Adherence app Reducing the complexity of the medication regime Positioning medication within their daily routine eg. by toothbrush Changing formulations Additional education regarding need for medication / timing of doses Referral to a social worker to assist with affordability of medicines Referral to a psychologist to explore deeper psychological issues regarding medicines taking The structure of each follow up adherence review will be the same as the first formal adherence review with the exception that the BMQ will only be repeated at the end of the one year follow-up and the socioeconomic and educational assessment will only be undertaken at the first assessment review. Every patient will have a formal adherence assessment at recruitment and then at 3, 6, 9 and 12 months. At the end of one year of follow-up, the specific benefits perceived by the patient of intensive adherence support from a pharmacist will be determined through a questionnaire. Baseline nonadherence will be measured at the first visit with the study pharmacist within two weeks of recruitment and then at 3, 6, 9 and 12 months. The IPV of their tacrolimus levels and their outpatient clinic nonattendance rate will be measured retrospectively in the 12 months prior to recruitment to the study and then prospectively at the end of the intervention year. The IPV is calculated from the tacrolimus levels measured for an individual patient using the coefficient of variance mathematical formula - Coefficient of variance (COV) defined as: SD x 100 / Mean. The outpatient clinic nonattendance for each participant will be taken from the hospital integrated computer system.

Official Title
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A Pharmacist Led, Patient Tailored Intervention to Improve Immunosuppressant Medication Adherence in Nonadherent Kidney Transplant Patients

Conditions
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Medication Adherence, Kidney Transplantation

Intervention / Treatment
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* Behavioral: Pharmacist led medication adherence interventions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult kidney transplant patients (18 years of age and above) Kidney transplant patients with an IPV of tacrolimus levels of greater than 18.15% in the previous 12 months Exclusion Criteria: Antibody incompatible transplants including patients with preformed HLA and blood group incompatible Previous rejection Donor specific antibody positive HIV positive patients Simultaneous pancreas and kidney patients Paediatric patients (less than 18 years of age)

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Medication adherence interventions<br>Pharmacist led medication adherence interventions which will be tailored to individual patient need | Behavioral: Pharmacist led medication adherence interventions<br>* Medication adherence interventions which will be tailored to individual patient need<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in immunosuppression medication adherence before and after the intervention | Medication adherence will be assessed and compared using the BAASIS questionnaire at recruitment and at the end of the study. The BAASIS questionnaire is validated for assessing immunosuppression nonadherence in transplant patients. Any patient answering yes to any of the questions is assessed to be nonadherent | One year | 
| Change in the median IPV before and after the intervention | Intrapatient variability of tacrolimus levels will be measured and compared | One year | 
| Change in outpatient clinic nonattendance rate before and after the intervention | Outpatient clinic nonattendance rate will be assessed and compared during the 12 months prior to recruitment to the study and during the study | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biopsy proven ACR / AMR | Number of patients who develop biopsy proven ACR/AMR | One year | 
| The number of readmissions | The number of readmissions and their reasons why during the study will be recorded | One year | 
| Donor specific antibody (DSA) or transplant glomerulopathy | Number of patients who develop a DSA or transplant glomerulopathy (CNI) toxicity or diabetic change on biopsy | One year | 
| Fibrosis, hyalinosis, calcineurin inhibitor (CNI) toxicity or diabetic change on toxicity | Number of patients who develop fibrosis, hyalinosis, calcineurin inhibitor | One year | 
| Graft loss | Number of patients who lose their graft | One year | 
| Death | Number of patients who die | One year | 
| Serum creatinine | Change in serum creatinine at the end of the study | One year | 
| eGFR | Change in eGFR at the end of the study | One year | 
| Proteinuria | Change in proteinuria at the end of the study | One year | 
| Haematocrit | Change in haematocrit at the end of the study | One year | 
| Haemoglobin | Change in haemoglobin at the end of the study | One year | 
| Albumin | Change in albumin at the end of the study | One year | 
| Tacrolimus levels | Change in tacrolimus levels at the end of the study | One year |