Comparison of efficacy and safety of extended-release versus immediate-release tacrolimus in renal transplant patients: a double-blind randomized controlled trial

To compare the efficacy and safety of extended release tacrolimus versus immediate release tacrolimus in adult de novo kidney transplant recipients during the first month after transplantation.

Prospective single center double blind parallel group randomized controlled trial with two study arms and a total sample size of 200 participants. Block randomization with permuted blocks of four was used. The six possible allocation sequences (AABB, ABAB, ABBA, BBAA, BABA, and BAAB) were generated using a random number table. Eligible participants were randomly allocated in a 1:1 ratio to either the intervention group or the control group based on the pre-generated randomization list.

The trial is conducted at the kidney transplantation center of Shiraz University of Medical Sciences. Participants, investigators, healthcare providers and outcome assessors are blinded. Follow up is performed during the first month after transplantation.

Adult patients aged 18 years or older undergoing first kidney transplantation from deceased brain dead donors are included. Main exclusion criteria are multiple organ transplantation, retransplantation, known hypersensitivity to tacrolimus, ABO incompatible transplantation, pregnancy or lactation.

Intervention group: Once-daily extended-release tacrolimus (Advagraf®, Astellas) initiated at 5 mg per day after kidney transplantation, with dose adjustment based on blood levels. Control group: Twice-daily immediate-release tacrolimus (Prograf®, Astellas) initiated at 2 mg twice daily after kidney transplantation, with dose adjustment based on blood levels.

Incidence of biopsy proven acute rejection; renal graft function assessed by serum creatinine; tacrolimus trough blood concentration.

Participants will be randomly allocated in a 1:1 ratio to one of two treatment groups using block randomization with permuted blocks of four. The six possible block permutations (AABB, ABAB, ABBA, BBAA, BABA, BAAB) will be used. Random numbers will be generated from a random number table, with numbers 1–6 corresponding to the block permutations; numbers 0, 7, 8, and 9 will be disregarded. Randomization will continue until the full sample size is assigned. The unit of randomization will be the individual participant. No stratified randomization will be applied. The randomization sequence will be generated in advance and used at enrollment. Allocation concealment will be maintained using the pre-generated randomization sequence.

This study is conducted as a double-blind randomized controlled trial. Study participants are blinded to treatment allocation and are not informed whether they receive extended-release tacrolimus (Advagraf®) or immediate-release tacrolimus (Prograf®). The principal investigator and all healthcare providers involved in patient care, including physicians and nurses, are blinded to group assignment throughout the study period. Randomization is performed using a pre-generated allocation sequence, which is kept confidential and is not accessible to investigators, healthcare providers, data collectors, or outcome assessors.

Deidentified individual participant data set including demographic variables, baseline clinical characteristics, intervention assignment, primary and secondary outcome measures collected during the first month after kidney transplantation.

The data will become available starting a few months after publication of the main study results

Deidentified data will be available to qualified researchers affiliated with academic or research institutions.

Data will be shared for scientific research purposes only. Requests must include a clear research proposal and will be reviewed by the principal investigator. Data use is limited to analyses consistent with the approved proposal.

Requests should be submitted via email to the principal investigator at Shiraz University of Medical Sciences. Communication will be conducted primarily by email. Email: nakisarasaei@gmail.com

Applicants must submit a written request including study objectives and analysis plan. Requests will be reviewed within approximately 2 weeks, and approved data will be shared after signing a data use agreement.