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Recruiting NCT06474273

TACKLE-IT Trial - Treat Acute T Cell Rejection With Evidence and Confidence in Kidney Transplant Recipients

Phase III Interventional Rejection; Transplant, Kidney Rejection; Transplant, Pancreas

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Methylprednisolone, Prednisone.
Who it may be relevant to
Registry conditions: Rejection; Transplant, Kidney, Rejection; Transplant, Pancreas. Basic parameters: from 2 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Australia, Canada, New Zealand
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Detailed description

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?'

Interventions

  • Drug Methylprednisolone
    IV Methylprednisolone
  • Drug Prednisone
    Oral prednisone augmentation

Primary outcome measures

  • Histological resolution of biopsy-proven acute rejection [Time frame: 12 weeks post-randomization]
  • Improvement in allograft function [Time frame: 12 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]
Secondary outcome measures (9)
  • Estimated glomerular filtration rate (eGFR) [Time frame: At 12, 24 and 48 weeks post-randomization]
  • All cause death and death-censored graft loss [Time frame: At 12 weeks post-randomization]
  • Urine albumin: creatinine ratios [Time frame: At 12, 24 and 48 weeks post-randomization]
  • Quality of life (QoL) [Time frame: Baseline (at randomization), 12 weeks , 24 weeks , and 48 weeks post-randomization]
  • Cancer [Time frame: Anytime from randomization to 48 weeks]
  • Trajectories of serum creatinine changes [Time frame: 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]
  • Infections (including those requiring antimicrobials and hospitalisation) [Time frame: Anytime from randomization to 48 weeks post-randomization]
  • Development of chronic fibrosis in the allograft [Time frame: Baseline to 12 weeks post-randomization]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Factorial
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

Canada · 13 centers
  • University of Calgary — Calgary
  • University of Alberta — Edmonton
  • Transplant Manitoba, adult — Winnipeg
  • Transplant Manitoba, pediatric — Winnipeg
  • Dalhousie University — Halifax
  • Western University — London
  • University of Toronto - St Michael Hospital — Toronto
  • University of Toronto - Hospital for Sick Kids — Toronto
  • … and 5 more centers
Australia · 11 centers
  • John Hunter Hospital — Lambton
  • Prince of Wales Hospital — Randwick
  • The Sydney Children's Hospital Network — Westmead
  • Westmead Hospital — Westmead
  • Queensland Children's Hospital — South Brisbane
  • Princess Alexandra Hospital — Woolloongabba
  • Royal Adelaide Hospital — Adelaide
  • Monash Medical Centre — Clayton
  • … and 3 more centers
New Zealand · 1 center
  • Auckland City Hospital — Grafton

Publications

  • Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, Goldberg A, Birk PE, Rush DN, Nickerson PW. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant. 2012 May;12(5):1157-67. doi: 10.1111/j.1600-6143.2012.04013.x. Epub 2012 Mar 19. PMID 22429309
  • Wiebe C, Kosmoliaptsis V, Pochinco D, Gibson IW, Ho J, Birk PE, Goldberg A, Karpinski M, Shaw J, Rush DN, Nickerson PW. HLA-DR/DQ molecular mismatch: A prognostic biomarker for primary alloimmunity. Am J Transplant. 2019 Jun;19(6):1708-1719. doi: 10.1111/ajt.15177. Epub 2018 Dec 15. PMID 30414349
  • Wiebe C, Rush DN, Gibson IW, Pochinco D, Birk PE, Goldberg A, Blydt-Hansen T, Karpinski M, Shaw J, Ho J, Nickerson PW. Evidence for the alloimmune basis and prognostic significance of Borderline T cell-mediated rejection. Am J Transplant. 2020 Sep;20(9):2499-2508. doi: 10.1111/ajt.15860. Epub 2020 Apr 9. PMID 32185878
  • Nickerson PW, Balshaw R, Wiebe C, Ho J, Gibson IW, Bridges ND, Rush DN, Heeger PS. A noninferiority design for a delayed calcineurin inhibitor substitution trial in kidney transplantation. Am J Transplant. 2021 Apr;21(4):1503-1512. doi: 10.1111/ajt.16311. Epub 2020 Oct 6. PMID 32956576
  • Rampersad C, Balshaw R, Gibson IW, Ho J, Shaw J, Karpinski M, Goldberg A, Birk P, Rush DN, Nickerson PW, Wiebe C. The negative impact of T cell-mediated rejection on renal allograft survival in the modern era. Am J Transplant. 2022 Mar;22(3):761-771. doi: 10.1111/ajt.16883. Epub 2021 Nov 24. PMID 34717048
  • Ho J, Okoli GN, Rabbani R, Lam OLT, Reddy VK, Askin N, Rampersad C, Trachtenberg A, Wiebe C, Nickerson P, Abou-Setta AM. Effectiveness of T cell-mediated rejection therapy: A systematic review and meta-analysis. Am J Transplant. 2022 Mar;22(3):772-785. doi: 10.1111/ajt.16907. Epub 2021 Dec 10. PMID 34860468
  • Nankivell BJ, Shingde M, Keung KL, Fung CL, Borrows RJ, O'Connell PJ, Chapman JR. The causes, significance and consequences of inflammatory fibrosis in kidney transplantation: The Banff i-IFTA lesion. Am J Transplant. 2018 Feb;18(2):364-376. doi: 10.1111/ajt.14609. Epub 2018 Jan 3. PMID 29194971
  • Tong A, Budde K, Gill J, Josephson MA, Marson L, Pruett TL, Reese PP, Rosenbloom D, Rostaing L, Warrens AN, Wong G, Craig JC, Crowe S, Harris T, Hemmelgarn B, Manns B, Tugwell P, Van Biesen W, Wheeler DC, Winkelmayer WC, Evangelidis N, Sautenet B, Howell M, Chapman JR. Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transp PMID 27500269

Identifiers

NCT: NCT06474273 · GWCT051274

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗