Finding the right steroid dose for acute T cell rejection after kidney or kidney–pancreas transplant

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

This trial will test whether lower doses of steroids work as well as higher doses to treat acute T cell–mediated rejection in people who have had a kidney or simultaneous kidney–pancreas transplant.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 540 (estimated)
• Ages: 2 Years and up
• Sex: All
• Sponsor: University of Sydney (other)
• Drugs / interventions: Rituximab, Eculizumab, prednisone
• Locations: 25 sites (Lambton, New South Wales and 24 other locations)
• Trial ID: NCT06474273 on ClinicalTrials.gov

What this trial studies

TACKLE-IT is a randomized, triple‑blind, 2x2 factorial, non‑inferiority trial embedded in registries that compares high versus low dose IV methylprednisolone and high versus low dose oral prednisone taper as first‑line therapy for acute T cell–mediated rejection (TCMR) after kidney or simultaneous pancreas–kidney transplant. The trial enrolls children (age ≥2 years) and adults with biopsy‑proven TCMR (≥ Banff borderline, minimum i1) and randomizes participants to one of four steroid dosing strategies. It is conducted across multiple transplant centers under international stakeholder and professional society collaboration, with standardized safety monitoring and graft outcome follow‑up. The primary aim is to determine the minimally acceptable steroid dose that preserves graft function while reducing steroid‑related harms.

Who should consider this trial

Good fit: Ideal candidates are people aged 2 years and older who have received a kidney or simultaneous kidney–pancreas transplant and have biopsy‑proven acute T cell–mediated rejection (≥ Banff borderline) and can provide informed consent and attend study visits.

Not a fit: Patients with mixed rejection, active or chronic active antibody‑mediated rejection, isolated vascular lesions without inflammation, certain concurrent renal diseases (e.g., recurrent GN or polyomavirus nephropathy), active infection or malignancy that preclude increased immunosuppression, or current use of other immunomodulators are excluded and would not be expected to benefit from this trial.

Why it matters

Potential benefit: If successful, the trial could allow doctors to use lower steroid doses that protect the transplant while reducing steroid side effects like infections, bone loss, cardiovascular risk, and weight gain.

How similar studies have performed: High‑dose steroids have been the longstanding standard for TCMR but there is limited high‑quality randomized evidence comparing dose levels, so this large factorial non‑inferiority design is relatively novel and aimed at filling that gap.

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.

Where this trial is running

Lambton, New South Wales and 24 other locations

• John Hunter Hospital — Lambton, New South Wales, Australia (NOT_YET_RECRUITING)
• Prince of Wales Hospital — Randwick, New South Wales, Australia (NOT_YET_RECRUITING)
• The Sydney Children's Hospital Network — Westmead, New South Wales, Australia (NOT_YET_RECRUITING)
• Westmead Hospital — Westmead, New South Wales, Australia (RECRUITING)
• Queensland Children's Hospital — South Brisbane, Queensland, Australia (RECRUITING)
• Princess Alexandra Hospital — Woolloongabba, Queensland, Australia (NOT_YET_RECRUITING)
• Royal Adelaide Hospital — Adelaide, South Australia, Australia (NOT_YET_RECRUITING)
• Monash Medical Centre — Clayton, Victoria, Australia (NOT_YET_RECRUITING)
• Royal Perth Children's hospital — Nedlands, Western Australia, Australia (NOT_YET_RECRUITING)
• Sir Charles Gairdner Hospital — Nedlands, Western Australia, Australia (NOT_YET_RECRUITING)
• Royal Perth Hospital — Perth, Western Australia, Australia (NOT_YET_RECRUITING)
• University of Calgary — Calgary, Alberta, Canada (NOT_YET_RECRUITING)
• University of Alberta — Edmonton, Alberta, Canada (NOT_YET_RECRUITING)
• Transplant Manitoba, adult — Winnipeg, Manitoba, Canada (NOT_YET_RECRUITING)
• Transplant Manitoba, pediatric — Winnipeg, Manitoba, Canada (NOT_YET_RECRUITING)
• Dalhousie University — Halifax, Nova Scotia, Canada (NOT_YET_RECRUITING)
• Western University — London, Ontario, Canada (NOT_YET_RECRUITING)
• University of Toronto - St Michael Hospital — Toronto, Ontario, Canada (NOT_YET_RECRUITING)
• University of Toronto - Hospital for Sick Kids — Toronto, Ontario, Canada (NOT_YET_RECRUITING)
• University of Toronto — Toronto, Ontario, Canada (NOT_YET_RECRUITING)
• McGill University — Montreal, Quebec, Canada (NOT_YET_RECRUITING)
• University of Montreal — Montreal, Quebec, Canada (NOT_YET_RECRUITING)
• University of Laval — Québec, Quebec, Canada (NOT_YET_RECRUITING)
• University of Saskatchewan — Saskatoon, Saskatchewan, Canada (NOT_YET_RECRUITING)
• Auckland City Hospital — Grafton, Auckland, New Zealand (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Germaine Wong, PhD, FRACP — University of Sydney
• Study coordinator: NHMRC Clinical Trials Centre THE UNIVERSITY OF SYDNEY

Conditions: Rejection, Transplant, Kidney, Transplant, Pancreas, Acute T cell mediated rejection