A Multicenter Randomized Controlled Trial to Treat Acute T Cell Mediated Rejection in Kidney and Kidney-Pancreas Transplant Recipients (TACKLE-IT)

August 26, 2026 updated by: University of Sydney

A Multicenter Randomized Controlled Trial to Treat Acute t Cell Mediated Rejection in Kidney and Kidney-pancreas Transplant Recipients

After a kidney or a 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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

TACKLE-IT is an international, multi-centre, 2x2 factorial, PROBE-style, 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?'

Study Type

Interventional

Enrollment (Estimated)

540

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Lambton, New South Wales, Australia, 2305
        • Not yet recruiting
        • John Hunter Hospital
        • Principal Investigator:
          • Thida Myint, FRACP
      • Randwick, New South Wales, Australia, 2031
        • Not yet recruiting
        • Prince of Wales Hospital
        • Principal Investigator:
          • Kenneth Yong, FRACP, PhD
      • Westmead, New South Wales, Australia, 2145
        • Recruiting
        • Westmead Hospital
        • Principal Investigator:
          • Germaine Wong, FRACP, Phd
      • Westmead, New South Wales, Australia, 2145
        • Not yet recruiting
        • The Sydney Children's Hospital Network
        • Principal Investigator:
          • Siah Kim, FRACP, PhD
    • Queensland
      • South Brisbane, Queensland, Australia, 2014
        • Recruiting
        • Queensland Children's Hospital
        • Principal Investigator:
          • Anna Francis, PhD, FRACP
      • Woolloongabba, Queensland, Australia, 4102
        • Not yet recruiting
        • Princess Alexandra Hospital
        • Principal Investigator:
          • Ryan Gately, MBBS, Mbiostat, MClinEpi
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Not yet recruiting
        • Royal Adelaide Hospital
        • Principal Investigator:
          • Michael Collins, FRACP, PhD
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Not yet recruiting
        • Monash Medical Centre
        • Principal Investigator:
          • William Mulley, FRACP, PhD
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
        • Not yet recruiting
        • Fiona Stanley Hospital
        • Principal Investigator:
          • Suda Swaminathan, MBBS, FRACP, MCR
      • Nedlands, Western Australia, Australia, 6009
        • Not yet recruiting
        • Sir Charles Gairdner Hospital
        • Principal Investigator:
          • Wai Lim, FRACP, PHD
      • Nedlands, Western Australia, Australia, 6009
        • Not yet recruiting
        • Royal Perth Children's hospital
        • Principal Investigator:
          • Nick Larkins, FRACP, PhD
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Not yet recruiting
        • Alberta Children's Hospital
        • Principal Investigator:
          • Lorraine Hamiwka, MD
      • Calgary, Alberta, Canada, T2N 4Z6
        • Not yet recruiting
        • Foothills Medical Centre
        • Principal Investigator:
          • Ngan Lam, MD, MSc
      • Edmonton, Alberta, Canada, T6G 2B7
        • Not yet recruiting
        • University of Alberta Hospital
        • Principal Investigator:
          • Emily Christie, MD, FRCPC
      • Edmonton, Alberta, Canada, T6G 1C9
        • Not yet recruiting
        • Stollery Children's Hospital
        • Principal Investigator:
          • Michelle Ruhl, MD, FRCPC
    • British Columbia
      • Vancouver, British Columbia, Canada, T6G 1C9
        • Not yet recruiting
        • BC Children's Hospital
        • Principal Investigator:
          • Tom Blydt-Hansen, MD
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A 1R9
        • Not yet recruiting
        • HSC Winnipeg Children's
        • Principal Investigator:
          • Aviva Goldberg, MD
      • Winnipeg, Manitoba, Canada
        • Not yet recruiting
        • Health Sciences Center, University of Manitoba
        • Principal Investigator:
          • Julie Ho, FRCPC
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 1V8
        • Not yet recruiting
        • QEII Health Sciences Centre, Nova Scotia Health Authority
        • Principal Investigator:
          • Amanda Vinson, MD
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • Not yet recruiting
        • London Health Science Centre
        • Principal Investigator:
          • Matthew Weir, MD, FRCPC
      • Toronto, Ontario, Canada, M5G 1E8
        • Not yet recruiting
        • University of Toronto - Hospital for Sick Kids
        • Principal Investigator:
          • Chia Wei Teoh, MB B.Ch., BAO, LRCSI, MRCPI
      • Toronto, Ontario, Canada, M5B 1W8
        • Not yet recruiting
        • St Mike's Hospital (Unity Health)
        • Principal Investigator:
          • Darren Yuen, MD, PhD
      • Toronto, Ontario, Canada, M5G 2N2
        • Not yet recruiting
        • Toronto General Hospital Research Institute (UHN)
        • Principal Investigator:
          • Joseph Kim, MD, PhD
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Not yet recruiting
        • Montreal Children's Hospital
        • Principal Investigator:
          • Beth Foster, MD, MSCE
      • Montreal, Quebec, Canada, H2X 0A9
        • Not yet recruiting
        • Centre Hospitalier de l'Universite de Montreal (CHUM)
        • Principal Investigator:
          • Daniel Fantus, MD, FRCPC
      • Montreal, Quebec, Canada, H3T 1C5
        • Not yet recruiting
        • CHU Ste-Justine
        • Principal Investigator:
          • Véronique Phan, MD
      • Montreal, Quebec, Canada, H3J 0A9
        • Not yet recruiting
        • Glen Site
        • Principal Investigator:
          • Shaifali Sandal, MD
      • Québec, Quebec, Canada, G1R 2J6
        • Not yet recruiting
        • CHU de Québec
        • Principal Investigator:
          • Sacha De Serres, MD, FRCPC
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7M 0Z9
        • Not yet recruiting
        • St. Paul's Hospital
        • Principal Investigator:
          • Rahul Manira, MD, FRCPC
  • New Zealand
    • Auckland
      • Grafton, Auckland, New Zealand, 1023
        • Not yet recruiting
        • Auckland City Hospital
        • Principal Investigator:
          • Helen Pilmore

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

    • Individuals with the following are eligible for inclusion:

      i. Concurrent acute TCMR and microvascular inflammation (MVI) defined as g+ptc, but without ABMR diagnosis.

ii. Concurrent acute TCMR and chronic active TCMR.

Exclusion Criteria:

Individuals meeting any of the following criteria will be excluded from participation:

  • Mixed rejection.
  • Active or chronic active ABMR.
  • Chronic active TCMR.
  • 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.

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?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lower dose IV methylprednisolone x Lower dose oral prednisone
Lower dose IV MP (250 mg daily x 3 days in adults or 150 mg/m² daily x 3, or to a max 250 mg/dose in children (<18 years), with lower dose (25mg daily x 7 days, or 15mg/m² x 7 days, or to a max 25mg/dose for those < 18 years ) oral prednisone augmentation then return to standard prednisone.
Drug: Methylprednisolone
IV Methylprednisolone
Other Names:
  • IV MP
Drug: Prednisone
Oral prednisone augmentation
Experimental: Lower dose IV methylprednisolone x Higher dose oral prednisone
Lower dose IV MP (250 mg daily x 3 in adults or 150 mg/m² daily x 3, or to a max 250 mg/dose in children (<18 years), with higher dose (50mg daily x 7, or 30mg/m² daily x 7, or to a max 50mg/dose for those < 18 years) oral prednisone augmentation then return to standard prednisone.
Drug: Methylprednisolone
IV Methylprednisolone
Other Names:
  • IV MP
Drug: Prednisone
Oral prednisone augmentation
Active Comparator: Higher dose IV methylprednisolone x lower dose oral prednisone
Higher dose IV MP (500mg daily x 3 in adults or 300 mg/m² daily x 3 or to a max 500 mg/dose in children (<18 years), with lower dose (25mg daily x 7 days, or 15mg/m² daily x 7 days, or to a max 25mg/dose for those < 18 years) oral prednisone augmentation then return to standard prednisone.
Drug: Methylprednisolone
IV Methylprednisolone
Other Names:
  • IV MP
Drug: Prednisone
Oral prednisone augmentation
Active Comparator: Higher dose IV methylprednisolone x higher dose oral prednisone
Higher dose IV MP (500 mg daily x 3 in adults or 300 mg/m² daily x 3 or to a max 500 mg/dose in children (<18 years), with higher dose (50mg daily x 7 days, or 30mg/m² daily x 7 days, or to a max 50mg/dose for those < 18 years) oral prednisone augmentation, then return to standard prednisone.
Drug: Methylprednisolone
IV Methylprednisolone
Other Names:
  • IV MP
Drug: Prednisone
Oral prednisone augmentation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histological resolution of biopsy-proven acute rejection
Time Frame: 12 weeks post-randomization
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 for clinical rejection; and defined by an average of at least 2 serum creatinine at baseline and at least 2 serum creatinine from 11-13 weeks
Time Frame: 11 to 13 weeks post-randomization
Reduction in serum creatinine ≥20% is defined as the relative reduction in serum creatinine from baseline and at 11-13 weeks after randomisation, in the absence of dialysis or achieving freedom from dialysis. Staff are required to record the serum creatinine at each visit; or dates and modality of dialysis initiation and / or discontinuation.
11 to 13 weeks post-randomization
Avoidance of rescue therapies within 12 weeks post-randomization to achieve histological resolution and/or improvement in allograft function
Time Frame: 12 weeks post-randomization
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

Outcome Measure
Measure Description
Time Frame
Urine albumin: creatinine ratios
Time Frame: At 12, 24 and 48 weeks post-randomization
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
Cancer
Time Frame: Anytime from randomization to 48 weeks
All types and sites
Anytime from randomization to 48 weeks
All cause death and death-censored graft loss
Time Frame: At 12 weeks post-randomization

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.

All-cause death also includes cause-specific death (infections, cancers, cardiovascular-related, and other causes of death) at 12 weeks after randomisation.
At 12 weeks post-randomization
Estimated glomerular filtration rate (eGFR)
Time Frame: At 12, 24 and 48 weeks post-randomization
  • 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
Trajectories of serum creatinine changes
Time Frame: From randomization to 48 weeks post-randomization
From randomization to 48 weeks post-randomization
Development of acute antibody mediated rejection (ABMR) and mixed rejection (concomitant ABMR + TCMR)
Time Frame: 48 weeks post-randomization
Development of acute antibody mediated rejection (ABMR) and mixed rejection (concomitant ABMR + TCMR) within 48 weeks after randomisation. ABMR and mixed rejection are defined according to the Banff 2022 criteria
48 weeks post-randomization
Development of chronic fibrosis in the allograft
Time Frame: Baseline to 12 weeks post-randomization
Development of chronic fibrosis in the allograft. This is defined as the absolute (Banff ci+ctscores) at 12 weeks
Baseline to 12 weeks post-randomization
Infections (all types and sites)
Time Frame: Anytime from randomization to 48 weeks post-randomization
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
Quality of life (QoL)
Time Frame: Baseline (at randomization), 12 weeks , 24 weeks , and 48 weeks post-randomization

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 2-7: EQ-5D-Y proxy version
  • Ages 8-17: EQ-5D-Y self-report 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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Steroid-related adverse effects
Time Frame: 3 days post randomisation, 7 days post randomisation, week 12 post-randomisation, week 24 post-randomisation and week 48 post-randomisation
Adaption from the Steroid Patient Reported Outcome (Steroid PRO).
3 days post randomisation, 7 days post randomisation, week 12 post-randomisation, week 24 post-randomisation and week 48 post-randomisation
Process evaluation: patients' and clinicians' perspectives on the treatment of acute TCMR
Time Frame: Anytime between week 12 and 48 of the trial
Semi-structured interviews will be conducted to elicit patients' perspectives and experiences of having acute TCMR, the adverse effects of the treatments. Health professionals' will also be interviewed to elicit their perspectives and experiences regarding the barriers, challenges, and enablers for implementing the intervention, the perceived benefits, and harms of the intervention and how the intervention should be delivered such that maximal interactions of the intervention are reached for the intended participants.
Anytime between week 12 and 48 of the trial
Integrative Box Risk Prediction Score (iBOX)
Time Frame: Week 13 to week 48 post-randomisation
Graft survival prediction will be assessed using the Integrative Box Risk Prediction Score (iBOX), a validated composite risk prediction tool for kidney transplant outcomes. The iBOX score integrates clinical, functional, and immunological parameters including serum creatinine, proteinuria, biopsy findings, and presence of donor-specific antibodies to estimate the risk of allograft failure. The iBox score essentially assigns a numerical value based on these parameters, indicating the risk of allograft loss (kidney transplant failure).
Week 13 to week 48 post-randomisation
Life participation
Time Frame: Randomisation, week 12 post-randomization, week 24 post-randomization and week 48 post-randomization

Life participation will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Ability to Participate in Social Roles and Activities - Short Form 4a (SF4a). This instrument measures perceived ability to perform usual social roles and activities.

Scores are reported as T-scores standardized to the general U.S. population (mean = 50, SD = 10).

  • Minimum score: 20
  • Maximum score: 80

Higher scores indicate better ability to participate in social roles and activities (i.e., a more favorable outcome).
Randomisation, week 12 post-randomization, week 24 post-randomization and week 48 post-randomization
Economic evaluation: Incremental costs and benefits
Time Frame: During the 52-week follow up period
Incremental costs and benefits (life years and quality adjusted life years gained) between the two treatment arms.
During the 52-week follow up period
Transplant biobank - analysis of TCMR treatment responders vs non-responders
Time Frame: Week 13 to week 48 post-randomization

To characterise and compare the T cell receptor (TCR) repertoire in transplant recipients who were responsive and not responsive to the various corticosteroid dosing strategies in acute TCMR.

  1. T cell receptor repertoire (Australia)
  2. Urine chemokines (Canada)
  3. HLA eplet analysis (Canada)
  4. Biopsy transcriptomics (B-HOT panel, Canada)
Week 13 to week 48 post-randomization
Transplant fibrosis ultrasound analysis
Time Frame: Week 13 to week 48 post-randomization
Correlation of ultrasound images collected at the time of kidney biopsy with histologic and clinical parameters (Canadian and Australian participating centers)
Week 13 to week 48 post-randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sydney

Collaborators

University of Manitoba

Investigators

  • Principal Investigator: Germaine Wong, PhD, FRACP, University of Sydney
  • Principal Investigator: Julie Ho, FRCPC, University of Manitoba

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 13, 2026

Primary Completion (Estimated)

June 1, 2030

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

June 19, 2024

First Submitted That Met QC Criteria

June 19, 2024

First Posted (Actual)

June 25, 2024

Study Record Updates

Last Update Posted (Actual)

August 31, 2026

Last Update Submitted That Met QC Criteria

August 26, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GWCT051274

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data collected for the study, including individual patient data and a data dictionary that defines each field in the data set, will be made available as deidentified participant data to researchers who propose to use the data for individual patient data meta-analysis. Data will be shared following approval of the proposal by the corresponding author and a signed data access agreement, beginning 2 years following main publication.

IPD Sharing Time Frame

Study protocol, SAP, ICF will be provided 3 months after registration. The Clinical study report and code will be provided after completion of the trial.

IPD Sharing Access Criteria

All IPD data arising from the trial will be shared 2 years after publication of the main results.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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