Incidence of Non Adherence to Treatment With Once-daily Formulation of Tacrolimus

Study Overview
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Brief Summary
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Aim The primary objective of this study is to compare medication adherence with medical therapy in patients receiving once-daily versus twice-daily tacrolimus regimens. Participants 60 adult renal transplant patients randomized 1:2 into twice-daily and once-daily tacrolimus groups Outcomes The primary outcome will be medication adherence to the once-daily and twice-daily regimens, measured in terms of implementation. Secondary outcomes will include graft and patient survival, renal function and adverse events. Follow up - 12 months

Detailed Description
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Following randomization (Day 0), 60 kidney transplant recipients of deceased or live kidneys will be randomized 1:2 into control and study- experimental arm. In control arm, named Tacrolimus BID arm, tacrolimus will be administered unchanged twice daily, morning and evening, while in study--experimental group named Tacrolimus QD- Advagraf, the Advagraf tacrolimus formulation will be administered once daily in the morning. In both groups doses will be adjusted to maintain tacrolimus trough levels at 10-12 ng/mL (days 1-28), 8-10 ng/mL (days 29-168) and 6-8 ng/mL thereafter for both treatment arms. Adjunct immunosuppression. Per-protocol rejection prophylaxis: All patients will receive Basiliximab induction at 20mg/bw on days 0 and 4. Methylprednisolone will be administered as intravenous bolus doses of 500 mg , 250 mg and 125 mg perioperatively, on days 0,1 and 2. Thereafter oral prednisone will be given: 20 mg/day (days 2-14), 15 mg/day (days 15-30), 10 mg/day (days 30-45), 7.5 mg/day (days 45-60) and 5 mg/day thereafter. MMF (2 g BID) will be started preoperatively, and reduced to 500 mg three times daily after 14-30 days. Rejection treatment: First-line acute rejection (AR) therapy with corticosteroids will be administered at the dose of 500 mg/day for 3 days. Mono- and/or polyclonal antibodies could be used as therapy for corticosteroid-resistant AR. First-line antibody therapy will be permitted only if biopsy indicate a severe vascular rejection (Banff IIB or III). Prophylactic treatment: Prophylactic antiviral treatment with oral ganciclovir 450 mg/day, and PCP prevention with 400 mg Sulfamethoxazole and 80 mg of Trimethoprim/day will be given to all patients on days 1-90. Endpoints. The primary endpoint: • adherence to the Tacrolimus administration defined as self-reported number of missed drug ingestions scored in Morisky Medical Adherence Assessment questionnaire Secondary endpoints: • efficacy failure defined as biopsy proven rejection, renal function, incidence of adverse events (AEs) and graft loss or death at the end of the analysis period Statistical analysis The data collected will be analyzed with Fisher's exact test, Wilcoxon' matched pair test and Kaplan-Meier's test

Official Title
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Evaluation of Incidence of Non Adherence to Treatment With Once-daily Formulation of Tacrolimus (ADVAGRAF) in Kidney Transplant Recipients

Conditions
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Medication Adherence

Intervention / Treatment
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* Drug: Tacrolimus BID
* Drug: Advagraf QD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age: 18 Years to 60 Years Gender: both Patients willing and able to participate in this study Patients who signed the informed consent form Patients who can visit the center based on the study schedule in the protocol Exclusion Criteria Patients who had previously received a kidney or another organ Patients, having positive lymphocyte cross-match Patients with PRA >50% Patients, who underwent desensitization Patients, who were diagnosed with cancer in the last five years Patients, who themselves or their donors have positive HIV, HBsAg, or anti-HCV test results Patients, who were treated with other investigated drugs within 30 days from their study enrollment Patients, who are planning to be pregnant, or who are pregnant or breastfeeding and who are not planning to use any contraceptive method during the study period. Patients who were addicted to drugs/alcohol within six months of their study enrollment Patients, who have a mental illness that makes appropriate communication with them impossible

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tacrolimus BID<br>20 patients receiving twice daily (BID) Tacrolimus | Drug: Tacrolimus BID<br>* Administration of Tacrolimus BID<br>* Other names: Prograf, Tacrocell;|
| Active Comparator: Advagraf QD<br>40 patients randomized to receive once daily (QD) Advagraf | Drug: Advagraf QD<br>* administration of Advagraf QD<br>* Other names: Advagraf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morisky Medical Adherence Assessment questionnaire | adherence to the Tacrolimus QD administration defined as self-reported number 9on scale from 1-8) of missed drug ingestions scored in Morisky Medical Adherence Assessment questionnaire | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| graft and patient survival | % of patients and grafts alive after 1st and 2nd year of study | 2 years | 
| gfr | gfr - glomerular filtration rate - a measure of renal function, in ml/min/1.73m2 | 2 years | 
| adverse events | percentage of patients with complications | 2years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non adherence, Tacrolimus, Advagraf