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TACKLE-IT Trial - Treat Acute T Cell Rejection With Evidence and Confidence in Kidney Transplant Recipients
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.
Study details:
TACKLE-IT is an international, multi-centre, 2x2 factorial, registry-based, single-blind, randomised controlled trial (RCT) that compares the effectiveness and safety of high vs low dose IV MP, and high vs low dose oral prednisone taper as the first-line therapy for acute TCMR in kidney and SPK transplant recipients. This RCT was conceived and developed through extensive consultation and collaboration with our key stakeholders, including transplant recipients with lived experience and the International TCMR Working Group with sponsorship by 4 international transplant societies (The Transplantation Society (TTS), American Society of Transplantation (AST), European Society of Transplantation (ESOT) and Transplant Society of Australia and New Zealand (TSANZ). TACKLE-IT is led by an international multi-disciplinary team of transplant health professionals, clinical trialists, biostatisticians, health economist, social scientist, consumers.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 2 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2024-12-01
Primary completion: 2029-12-01
Study completion finish: 2029-12-01
Study type
TREATMENT
Phase
PHASE4
Trial ID
NCT06474273
Intervention or treatment
DRUG: Methylprednisolone
DRUG: Prednisone
Conditions
- • Rejection; Transplant, Kidney
- • Rejection; Transplant, Pancreas
Find a site
Closest Location:
Royal Adelaide Hospital
Research sites nearby
Select from list below to view details:
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Monash Medical Centre
Clayton, Victoria, Australia
John Hunter Hospital
Lambton, New South Wales, Australia
Prince of Wales Hospital
Randwick, New South Wales, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Lower dose IV methylprednisolone x Lower dose oral prednisone
| DRUG: Methylprednisolone
|
EXPERIMENTAL: Lower dose IV methylprednisolone x Higher dose oral prednisone
| DRUG: Methylprednisolone
|
ACTIVE_COMPARATOR: Higher dose IV methylprednisolone x lower dose oral prednisone
| DRUG: Methylprednisolone
|
ACTIVE_COMPARATOR: Higher dose IV methylprednisolone x higher dose oral prednisone
| DRUG: Methylprednisolone
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| 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
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| 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 |
Frequently Asked Questions
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