A Multicenter Randomized Controlled Trial to Treat Acute T Cell Mediated Rejection in Kidney and Kidney-Pancreas 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 is 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, triple-blind, non-inferiority registry-embedded, 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.
TACKLE-IT will address the critical unmet need and resolve a decades-long unanswered question, 'What is the minimally acceptable, safe and effective steroid dose for the treatment of acute TCMR in kidney and SPK transplant recipients?'.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Participants or their legal guardian must be able to understand and provide written informed consent
- Stated willingness to comply with all study procedures and availability for the duration of the study
- All ethnic and gender groups will have equal access to the study
- All children (aged 2+ years) and adults who have received a kidney or SPK transplant with biopsy proven acute TCMR (≥ Banff borderline (minimum i1 score) whether clinical or subclinical)
Exclusion criteria
- Mixed rejection
- Active or chronic active ABMR
- Chronic active TCMR. *Patients with concomitant acute TCMR and chronic active TCMR will not be excluded from the trial
- Isolated v1 without inflammation
- Concurrent renal disease, such as recurrent glomerulonephritis or polyomavirus nephropathy
- Active malignancies or active infection that preclude immunosuppression augmentation
- Use of other immunomodulatory agents, including, but not limited to, Rituximab, Anti-TNF monoclonal antibody, Belatacept, Abatacept, Janus kinase inhibitors, Eculizumab, Pegcetacoplan
- Enrolment in other interventional drug trials
- Use of other investigational agents
- Unable to adhere to the study protocol
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT06474273
Intervention or treatment
DRUG: Methylprednisolone
DRUG: Prednisone
Conditions
- Rejection; Transplant, Kidney
- Rejection; Transplant, Pancreas
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
John Hunter Hospital
Select from list below to view details:
John Hunter Hospital
Lambton, New South Wales, Australia
Prince of Wales Hospital
Randwick, New South Wales, Australia
The Sydney Children's Hospital Network
Westmead, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
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Who is running the clinical trial?
University of Sydney
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, Drug: Prednisone |
EXPERIMENTAL: Lower dose IV methylprednisolone x Higher dose oral prednisone
| Drug: Methylprednisolone, Drug: Prednisone |
ACTIVE_COMPARATOR: Higher dose IV methylprednisolone x lower dose oral prednisone
| Drug: Methylprednisolone, Drug: Prednisone |
ACTIVE_COMPARATOR: Higher dose IV methylprednisolone x higher dose oral prednisone
| Drug: Methylprednisolone, Drug: Prednisone |
What is the study measuring?
Primary Outcome
| Measure | Description | 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 randomisation , ii) serum creatinine at the time of randomisation, iii) serum creatinine at the time of the first IV MP. Reduction in serum creatinine ≥20% is defined as the relative reduction in serum creatinine from baseline and at 12 weeks after randomisation. | 12 weeks post-randomization |
| Avoidance of rescue therapies within 12 weeks post-randomization 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 randomization. | 12 weeks post-randomization |
Secondary Outcome
| Measure | Description | 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 \&amp;amp;amp;amp;amp;amp;amp;lt; 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 |
| Quality of life (QoL) | QoL will be assessed using the EuroQol-5 Dimension-5 Level (EQ-5D-5L) for adult participants (aged ≥18 years). For paediatric participants (aged 2-17 years), age-appropriate versions of the EuroQol Youth version (EQ-5D-Y) will be used as follows: * Ages 4-7: EQ-5D-Y proxy version * Ages 8-11: EQ-5D-Y self-report version * Ages 12-15: EQ-5D-Y self-report version * Age ≥16: EQ-5D-5L adult version Both the EQ-5D-5L and EQ-5D-Y report utility scores ranging from -0.281 to 1 (EQ-5D-5L UK value set) and -0.109 to 1 (EQ-5D-Y, proxy or self-report), where 1 represents perfect health, 0 represents a health state equivalent to death, and negative scores represent health states worse than death. Higher scores indicate better health-related quality of life. | Baseline (at randomization), 12 weeks , 24 weeks , and 48 weeks post-randomization |
| Cancer | All types and sites | Anytime from randomization to 48 weeks |
| 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. | From randomization to 48 weeks post-randomization |
| 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 |
| Infections (including those requiring antimicrobials and hospitalisation) | All types and number of events related to infections that required antimicrobials and hospitalisation for infections will be recorded. | Anytime from randomization to 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-randomization |
References
Clinical Trials Gov: A Multicenter Randomized Controlled Trial to Treat Acute T Cell Mediated Rejection in Kidney and Kidney-Pancreas Transplant RecipientsOther trials to consider
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