Clinical trial NCT02805842: Incidence of Non Adherence to Treatment With Once-daily Formulation of Tacrolimus
Official title: Evaluation of Incidence of Non Adherence to Treatment With Once-daily Formulation of Tacrolimus (ADVAGRAF) in Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Medication Adherence
Keywords: non adherence
Tacrolimus
Advagraf
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
Collaborators: name: Astellas Pharma Inc
name: Teva Pharma
First posted: 2016-06-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Morisky Medical Adherence Assessment questionnaire
timeFrame: 2 years
Secondary outcomes:
measure: graft and patient survival
timeFrame: 2 years
measure: gfr
timeFrame: 2 years
measure: adverse events
timeFrame: 2years
Other outcomes:
Locations:
city: Petach Tikva
country: Israel
facility: Rabin Med Ctr
Study officials:
affiliation: Rabin Med CTR
name: Eyan Mor, MD
role: STUDY_DIRECTOR
References:
citation: Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 12;9(9):CD012854. doi: 10.1002/14651858.CD012854.pub2.