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Studies

Interventional Recruiting Phase 3

NCT06474273 on ClinicalTrials.gov

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

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

  • Sponsor: University of Sydney
  • Collaborators: University of Manitoba
  • Enrollment: 540 (Estimated)
  • Study start: 2026-03-13 (Actual)
  • Primary completion: 2030-06-01 (Estimated)
  • Study completion: 2030-06-01 (Estimated)
  • Allocation: Randomized
  • InterventionModel: Factorial
  • InterventionModelDescription: International, multicentre, 2x 2 factorial, PROBE-style, non-inferiority, registry-embedded RCT of lower vs higher dose IV MP (methylprednisolone), and lower vs higher oral prednisone dose augmentation. The IV methylprednisolone component is open-label. The oral prednisone component remains triple-blinded, and all primary and key secondary endpoints will be assessed using blinded central adjudication.
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • PrimaryPurpose: Treatment

Brief Summary

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.

Conditions

  • Rejection; Transplant, Kidney
  • Rejection; Transplant, Pancreas

Intervention / Treatment

  • Drug: Methylprednisolone
  • Drug: Prednisone

Primary Outcome Measures

  • Histological resolution of biopsy-proven acute rejection (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.
  • 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 (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.
  • Avoidance of rescue therapies within 12 weeks post-randomization to achieve histological resolution and/or improvement in allograft function (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.

Countries

Australia, Canada, New Zealand

Locations and Investigators

  • John Hunter Hospital, Lambton, Australia (Not yet recruiting)
    • Thida Myint, FRACP (Principal Investigator)
  • Prince of Wales Hospital, Randwick, Australia (Not yet recruiting)
    • Kenneth Yong, FRACP, PhD (Principal Investigator)
  • The Sydney Children's Hospital Network, Westmead, Australia (Not yet recruiting)
    • Siah Kim, FRACP, PhD (Principal Investigator)
  • Westmead Hospital, Westmead, Australia (Recruiting)
    • Germaine Wong, FRACP, Phd (Principal Investigator)
  • Queensland Children's Hospital, South Brisbane, Australia (Recruiting)
    • Anna Francis, PhD, FRACP (Principal Investigator)
  • Princess Alexandra Hospital, Woolloongabba, Australia (Not yet recruiting)
    • Ryan Gately, MBBS, Mbiostat, MClinEpi (Principal Investigator)
  • Royal Adelaide Hospital, Adelaide, Australia (Not yet recruiting)
    • Michael Collins, FRACP, PhD (Principal Investigator)
  • Monash Medical Centre, Clayton, Australia (Not yet recruiting)
    • William Mulley, FRACP, PhD (Principal Investigator)
  • Fiona Stanley Hospital, Murdoch, Australia (Not yet recruiting)
    • Suda Swaminathan, MBBS, FRACP, MCR (Principal Investigator)
  • Royal Perth Children's hospital, Nedlands, Australia (Not yet recruiting)
    • Nick Larkins, FRACP, PhD (Principal Investigator)
  • Sir Charles Gairdner Hospital, Nedlands, Australia (Not yet recruiting)
    • Wai Lim, FRACP, PHD (Principal Investigator)
  • Foothills Medical Centre, Calgary, Canada (Not yet recruiting)
    • Ngan Lam, MD, MSc (Principal Investigator)
  • Alberta Children's Hospital, Calgary, Canada (Not yet recruiting)
    • Lorraine Hamiwka, MD (Principal Investigator)
  • Stollery Children's Hospital, Edmonton, Canada (Not yet recruiting)
    • Michelle Ruhl, MD, FRCPC (Principal Investigator)
  • University of Alberta Hospital, Edmonton, Canada (Not yet recruiting)
    • Emily Christie, MD, FRCPC (Principal Investigator)
  • BC Children's Hospital, Vancouver, Canada (Not yet recruiting)
    • Tom Blydt-Hansen, MD (Principal Investigator)
  • HSC Winnipeg Children's, Winnipeg, Canada (Not yet recruiting)
    • Aviva Goldberg, MD (Principal Investigator)
  • Health Sciences Center, University of Manitoba, Winnipeg, Canada (Not yet recruiting)
    • Julie Ho, FRCPC (Principal Investigator)
  • QEII Health Sciences Centre, Nova Scotia Health Authority, Halifax, Canada (Not yet recruiting)
    • Amanda Vinson, MD (Principal Investigator)
  • London Health Science Centre, London, Canada (Not yet recruiting)
    • Matthew Weir, MD, FRCPC (Principal Investigator)
  • St Mike's Hospital (Unity Health), Toronto, Canada (Not yet recruiting)
    • Darren Yuen, MD, PhD (Principal Investigator)
  • University of Toronto - Hospital for Sick Kids, Toronto, Canada (Not yet recruiting)
    • Chia Wei Teoh, MB B.Ch., BAO, LRCSI, MRCPI (Principal Investigator)
  • Toronto General Hospital Research Institute (UHN), Toronto, Canada (Not yet recruiting)
    • Joseph Kim, MD, PhD (Principal Investigator)
  • Centre Hospitalier de l'université de Montréal (CHUM), Montreal, Canada (Not yet recruiting)
    • Daniel Fantus, MD, FRCPC (Principal Investigator)
  • Glen Site, Montreal, Canada (Not yet recruiting)
    • Shaifali Sandal, MD (Principal Investigator)
  • CHU Ste-Justine, Montreal, Canada (Not yet recruiting)
    • Véronique Phan, MD (Principal Investigator)
  • Montreal Children's Hospital, Montreal, Canada (Not yet recruiting)
    • Beth Foster, MD, MSCE (Principal Investigator)
  • CHU de Quebec, Québec, Canada (Not yet recruiting)
    • Sacha De Serres, MD, FRCPC (Principal Investigator)
  • St. Paul's Hospital, Saskatoon, Canada (Not yet recruiting)
    • Rahul Manira, MD, FRCPC (Principal Investigator)
  • Auckland City Hospital, Grafton, New Zealand (Not yet recruiting)
    • Helen Pilmore (Principal Investigator)

Study Officials