TACKLE-IT Trial - Treat Acute T Cell Rejection With Evidence and Confidence in Kidney Transplant Recipients
NCT Number: NCT06474273
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Rejection; Transplant, Kidney|Rejection; Transplant, Pancreas
Interventions: DRUG: Methylprednisolone|DRUG: Prednisone
Sponsor: University of Sydney
Collaborators: University of Manitoba
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 540
Study Design: Allocation: RANDOMIZED|Intervention Model: FACTORIAL|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-12
Completion Date: 2029-12
Locations: John Hunter Hospital, Lambton, New South Wales, 2305, Australia|Prince of Wales Hospital, Randwick, New South Wales, 2031, Australia|The Sydney Children's Hospital Network, Westmead, New South Wales, 2145, Australia|Westmead Hospital, Westmead, New South Wales, 2145, Australia|Queensland Children's Hospital, South Brisbane, Queensland, 2014, Australia|Princess Alexandra Hospital, Woolloongabba, Queensland, 4102, Australia|Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia|Monash Medical Centre, Clayton, Victoria, 3168, Australia|Royal Children's Hospital Melbourne, Parkville, Victoria, 3052, Australia|Royal Perth Children's hospital, Nedlands, Western Australia, 6009, Australia|Sir Charles Gairdner Hospital, Nedlands, Western Australia, 6009, Australia|Royal Perth Hospital, Perth, Western Australia, 6000, Australia|University of Calgary, Calgary, Alberta, T2N 1N4, Canada|Transplant Manitoba, adult, Winnipeg, Manitoba, R3A 1R9, Canada|Transplant Manitoba, pediatric, Winnipeg, Manitoba, R3A 1R9, Canada|Western University, London, Ontario, N6A 3K7, Canada|University of Toronto, Toronto, Ontario, M5S 1A1, Canada|McGill University, Montréal, Quebec, H3A 0G4, Canada|University of Montreal, Montréal, Quebec, H3T 1J4, Canada|University of Laval, Québec, Quebec, G1V 0B4, Canada|University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5A2, Canada|Auckland City Hospital, Grafton, Auckland, 1023, New Zealand

Summary:
After a kidney or a simultaneous kidney-pancreas transplant, some patients may face problems with their new organs. This happens because the body sometimes makes a mistake and tries to get rid of the organ. This problem is called "rejection". One type of rejection is known as Acute T cell mediated rejection (TCMR). This can lead to many problems or even stop the transplant from working.

Doctors give strong steroids to treat this problem, but there are no rules for how much steroid to give. Too much steroids can cause problems like heart and bone problems, bad infections, and weight gain. That's why we need to find the right dose of steroids for each person to treat this.

TACKLE-IT is a study that will try to find the right steroid dose for treating rejection.

Primary Outcome Measures: Histological resolution of biopsy-proven acute rejection, Histological resolution of biopsy-proven acute rejection is defined by the absence of any biopsy-proven acute rejection (BPAR) on follow-up biopsy, including \<Banff Borderline (i1 t1), mixed rejection, ABMR and chronic active TCMR using Banff 2022 criteria., 12 weeks post-randomization|Improvement in allograft function, Baseline serum creatinine is defined by an average of three serum creatinine measures: i) first serum creatinine preceding randomization , ii) serum creatinine at the time of randomisation, iii) serum creatinine at the time of the first IV MP. If randomisation and treatment with the first IV MP occur on the same day, then only a single serum creatinine will be required.

Reduction in serum creatinine ≥20% is defined as the relative reduction in serum creatinine from baseline and at 12 weeks after randomisation. Staff are required to record all available serum creatinine from randomization to 12 weeks, and then at each study visit., 12 weeks post-randomization|Avoidance of rescue therapies within 12 weeks post-randomisation to achieve histological resolution and/or improvement in allograft function, Use of rescue therapy is defined as: the use of any adjunctive T and B cell depleting therapies such as intravenous thymoglobulin, alemtuzumab, bortezomib, or rituximab, or additional doses of IV MP within the first 12 weeks after randomisation., 12 weeks post-randomization
Secondary Outcome Measures: Estimated glomerular filtration rate (eGFR), * Absolute eGFR (2021 CKD-EPI eGFR without race modifier for adults, and the CKiD U25 equation to estimate GFR in children \< 18 years) 12, 24 and 48 weeks.
* Decline in eGFR (slope) from randomization to 48 weeks., At 12, 24 and 48 weeks post-randomization|All cause death and death-censored graft loss, All cause death and death-censored graft loss have been identified as the core outcomes for kidney transplant recipients. However, death and death-censored graft loss are anticipated to have a very low incidence at the 12 weeks post-randomization primary outcome ascertainment and were therefore not included in the primary composite outcome. They will be reported as principal secondary endpoints., At 12 weeks post-randomization|Urine albumin: creatinine ratios, Urine ACR is measured as standard of care. Rationale: ACR screens for graft dysfunction and is a marker for graft outcomes, At 12, 24 and 48 weeks post-randomization|Trajectories of serum creatinine changes, \*an average of three serum creatinine measures will be considered as baseline serum creatinine measures: i) first serum creatinine preceding randomization, ii) serum creatinine at the time of randomisation, iii) serum creatinine at the time of the first IV MP. If randomisation and treatment with the first IV MP occur on the same day, then only a single serum creatinine will be required.), From randomization to 48 weeks|Development of acute antibody mediated rejection (ABMR) and mixed rejection (concomitant ABMR + TCMR), ABMR and mixed rejection are defined according to the Banff 2022 criteria, 48 weeks post randomization|Development of chronic fibrosis in the allograft, This is defined as a change in ci and ct scores (a marker of interstitial fibrosis and tubular atrophy, measurement of fibrosis, defined by the Banff 2022 criteria), Baseline to 12 weeks post-randomisation|Infections (requiring antimicrobials and hospitalisation), The types and number of events related to infections that required antimicrobials and hospitalisation for infections will be recorded., Anytime from randomization to 48 weeks|Quality of life (QoL), QoL will be assessed using the EuroQol-5 Dimension-5 Level (EQ-5D-5L) for adults (participants ≥18 years), and ED-5D-Y for paediatric participants (aged between 2- 18 years), At randomization, 12 weeks post-randomization, 24 weeks post-randomization, and 48 weeks post-randomization|Infections (all types), All types, Anytime from randomization to 48 weeks|Cancer, All types and sites, Anytime from randomization to 48 weeks