protocolSection identificationModule nctId: NCT06268769, orgStudyIdInfo id: TaC:Drop, secondaryIdInfos id: 2023-503531-18-00, type: OTHER, domain: EUCT Number, briefTitle: Tacrolimus C:D Ratio Measured in Renal Transplant Recipients Treated With Once-daily Prolonged-release Drugs, acronym: TaC:Drop, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-03-09, primaryCompletionDateStruct date: 2026-12, completionDateStruct date: 2029-09, studyFirstPostDateStruct date: 2024-02-20, lastUpdatePostDateStruct date: 2024-04-08, sponsorCollaboratorsModule leadSponsor name: Edward Geissler, class: OTHER, collaborators name: Chiesi Pharmaceuticals GmbH, descriptionModule briefSummary: The goal of this clinical trial is to compare the bioavailability and practicability of two different formulations of tacrolimus in kidney transplant recipients. The main objective is to demonstrate that Envarsus® (test drug) has superior (higher) oral bioavailability compared with Advagraf™ (comparator drug) at 12 weeks after kidney transplantation. The trial also aims to compare the practicability (handling) of the two drugs using a series of pharmacokinetic parameters and to explore the relationship between drug bioavailability and long-term clinical outcomes, with a special focus on dose-dependent adverse reactions, measured until 3 years post-transplantation. The trial incorporates a pharmacokinetic sub-study designed to profile the peak tacrolimus blood concentration up to 6 hours after drug intake on the day of the 12-week study visit., conditionsModule conditions: Immunosuppression, designModule studyType: INTERVENTIONAL, phases: PHASE4, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: A dynamic allocation technique assigns participants in a 1:1 ratio to one of two treatment arms: Envarsus tablets (test IMP) or Advagraf capsules (comparator IMP). Randomisation is stratified by two factors: a) trial site, in order to minimise systematic treatment bias at the level of the trial centre and reduce the influence of inter-centre variability, and b) participation in the optional pharmacokinetic sub-study, in order to ensure an equal representation of Envarsus- and Advagraf-treated patients in the sub-study., primaryPurpose: PREVENTION, maskingInfo masking: NONE, enrollmentInfo count: 300, type: ESTIMATED, armsInterventionsModule interventions name: Tacrolimus Pill, interventions name: Tacrolimus capsule, outcomesModule primaryOutcomes measure: Dose-normalised blood trough level of tacrolimus (concentration/dose ratio), secondaryOutcomes measure: Time to reach the first trough level in target range, secondaryOutcomes measure: Proportion of patients with trough levels lower, within, or higher than the target range, secondaryOutcomes measure: Mean tacrolimus trough level and inter-patient variability (range) of tacrolimus trough levels, secondaryOutcomes measure: Mean daily dose of tacrolimus and inter-patient variability (range) of tacrolimus daily dose, secondaryOutcomes measure: Tacrolimus concentration/dose (C/D) ratio, secondaryOutcomes measure: Intra-patient variability of C/D ratio and daily dose, secondaryOutcomes measure: Treatment failure rate, secondaryOutcomes measure: Time to treatment failure after transplantation, secondaryOutcomes measure: Incidence rate, severity and time to clinically-confirmed biopsy-proven acute rejection, secondaryOutcomes measure: Incidence rate of graft failure, secondaryOutcomes measure: Mortality rate, secondaryOutcomes measure: Graft function measured by eGFR (estimated glomerular filtration rate), secondaryOutcomes measure: Incidence rate of for-cause biopsies, secondaryOutcomes measure: Incidence rate of acute rejection episodes requiring treatment, secondaryOutcomes measure: Incidence rate of steroid-resistant episodes of biopsy-proven acute rejection, secondaryOutcomes measure: Incidence rate of delayed graft function, secondaryOutcomes measure: Incidence rate of primary non-function of the renal allograft, secondaryOutcomes measure: Incidence of hepatotoxicity, secondaryOutcomes measure: Incidence of CMV and BKV infection (including organ manifestation, if relevant), secondaryOutcomes measure: Incidence, type, severity and seriousness of adverse reactions (ARs), secondaryOutcomes measure: Blood pressure, secondaryOutcomes measure: Incidence of de novo tremor, secondaryOutcomes measure: Incidence of gastrointestinal disorders requiring diagnostic investigation, secondaryOutcomes measure: Incidence of new onset diabetes mellitus after transplantation (NODAT), secondaryOutcomes measure: Recurrence of primary kidney disease, secondaryOutcomes measure: Incidence of de novo DSA, secondaryOutcomes measure: Patient-reported health-related quality-of-life measured using the Kidney Transplant Questionnaire-34 (KTQ-34), secondaryOutcomes measure: Doses and duration of glucocorticosteroid treatment, secondaryOutcomes measure: Dose of mycophenolate, secondaryOutcomes measure: Incidence and time to study treatment discontinuation, secondaryOutcomes measure: Incidence, time to and reason for patient withdrawal from study, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Charité Universitätsmedizin, Department of Nephrology and Medical Intensive Care, status: NOT_YET_RECRUITING, city: Berlin, zip: 10117, country: Germany, contacts name: Klemens Budde, Prof. Dr., role: CONTACT, geoPoint lat: 52.52437, lon: 13.41053, locations facility: University Hospital Dresden, Division of Nephrology, status: RECRUITING, city: Dresden, zip: 01307, country: Germany, contacts name: Christian Hugo, Prof. Dr., role: CONTACT, geoPoint lat: 51.05089, lon: 13.73832, locations facility: University Medical Center Hamburg-Eppendorf, Internal Medicine III (Nephrology, Rheumatology, Endocrinology), status: NOT_YET_RECRUITING, city: Hamburg, zip: 20251, country: Germany, contacts name: Malte A. Kluger, PD Dr., role: CONTACT, geoPoint lat: 53.57532, lon: 10.01534, locations facility: University Medical Center of the Johannes Gutenberg University Mainz, Medical Clinic I. (Nephrology), status: NOT_YET_RECRUITING, city: Mainz, zip: 55131, country: Germany, contacts name: Julia Weinmann-Menke, Prof. Dr., role: CONTACT, geoPoint lat: 49.98419, lon: 8.2791, locations facility: University Hospital Regensburg, Department of Nephrology, status: RECRUITING, city: Regensburg, zip: 93053, country: Germany, contacts name: Edward K. Geissler, PhD, role: CONTACT, phone: +49 941 944, phoneExt: 6961, email: edward.geissler@ukr.de, contacts name: Bernhard Banas, MD, PhD, role: CONTACT, phone: +49 941 944, phoneExt: 7301, email: bernhard.banas@ukr.de, geoPoint lat: 49.01513, lon: 12.10161, hasResults: False