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

NCT ID: NCT06474273

Last Updated: 2025-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

540 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-30

Study Completion Date

2030-06-30

Brief Summary

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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

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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?'

Conditions

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Rejection; Transplant, Kidney Rejection; Transplant, Pancreas

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

2x2 factorial, triple-blind, non-inferiority, RCT of lower vs higher dose IV MP (methylprednisolone), and lower vs higher oral prednisone dose augmentation.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
As a triple-blind study, all investigators, research staff, clinicians, outcome assessors, data analysts and participants will be blinded to the allocation of the IV MP treatment comparisons.

All key stakeholders including the global steering committee, the site investigators, and the trial management committee (TMC) will remain blinded to the individual patient randomization and the aggregate data that may reveal the unblinded outcomes. All researchers responsible for the analysis will remain blinded for the duration of the trial. Only the members of the Data Safety Monitoring Board (DSMB) and the independent statistician supporting their work will be unblinded prior to study completion.

Study Groups

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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 for those \< 18 years ) oral prednisone augmentation then return to standard prednisone.

Group Type EXPERIMENTAL

Methylprednisolone

Intervention Type DRUG

IV Methylprednisolone

Prednisone

Intervention Type DRUG

Oral prednisone augmentation

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 for those \< 18 years) oral prednisone augmentation then return to standard prednisone.

Group Type EXPERIMENTAL

Methylprednisolone

Intervention Type DRUG

IV Methylprednisolone

Prednisone

Intervention Type DRUG

Oral prednisone augmentation

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 for those \< 18 years) oral prednisone augmentation then return to standard prednisone.

Group Type ACTIVE_COMPARATOR

Methylprednisolone

Intervention Type DRUG

IV Methylprednisolone

Prednisone

Intervention Type DRUG

Oral prednisone augmentation

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 for those \< 18 years) oral prednisone augmentation, then return to standard prednisone.

Group Type ACTIVE_COMPARATOR

Methylprednisolone

Intervention Type DRUG

IV Methylprednisolone

Prednisone

Intervention Type DRUG

Oral prednisone augmentation

Interventions

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Methylprednisolone

IV Methylprednisolone

Intervention Type DRUG

Prednisone

Oral prednisone augmentation

Intervention Type DRUG

Other Intervention Names

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IV MP

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Manitoba

OTHER

Sponsor Role collaborator

University of Sydney

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Germaine Wong, PhD, FRACP

Role: PRINCIPAL_INVESTIGATOR

University of Sydney

Julie Ho, FRCPC

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Locations

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John Hunter Hospital

Lambton, New South Wales, Australia

Site Status

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status

The Sydney Children's Hospital Network

Westmead, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

Royal Perth Children's hospital

Nedlands, Western Australia, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

University of Calgary

Calgary, Alberta, Canada

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

Transplant Manitoba, adult

Winnipeg, Manitoba, Canada

Site Status

Transplant Manitoba, pediatric

Winnipeg, Manitoba, Canada

Site Status

Dalhousie University

Halifax, Nova Scotia, Canada

Site Status

Western University

London, Ontario, Canada

Site Status

University of Toronto - St Michael Hospital

Toronto, Ontario, Canada

Site Status

University of Toronto - Hospital for Sick Kids

Toronto, Ontario, Canada

Site Status

University of Toronto

Toronto, Ontario, Canada

Site Status

McGill University

Montreal, Quebec, Canada

Site Status

University of Montreal

Montreal, Quebec, Canada

Site Status

University of Laval

Québec, Quebec, Canada

Site Status

University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status

Auckland City Hospital

Grafton, Auckland, New Zealand

Site Status

Countries

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Australia Canada New Zealand

Central Contacts

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Chandana Guha, MEcon

Role: CONTACT

+61 9845 1229

Angela Rejuso, BMSc(Hons)

Role: CONTACT

References

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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.

Reference Type BACKGROUND
PMID: 22429309 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30414349 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32185878 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32956576 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34717048 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34860468 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29194971 (View on PubMed)

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 Transplantation. Transplant Direct. 2016 May 19;2(6):e79. doi: 10.1097/TXD.0000000000000593. eCollection 2016 Jun.

Reference Type BACKGROUND
PMID: 27500269 (View on PubMed)

Sautenet B, Tong A, Chapman JR, Warrens AN, Rosenbloom D, Wong G, Gill J, Budde K, Rostaing L, Marson L, Josephson MA, Reese PP, Pruett TL, Evangelidis N, Craig JC. Range and Consistency of Outcomes Reported in Randomized Trials Conducted in Kidney Transplant Recipients: A Systematic Review. Transplantation. 2018 Dec;102(12):2065-2071. doi: 10.1097/TP.0000000000002278.

Reference Type BACKGROUND
PMID: 29781954 (View on PubMed)

Sautenet B, Tong A, Manera KE, Chapman JR, Warrens AN, Rosenbloom D, Wong G, Gill J, Budde K, Rostaing L, Marson L, Josephson MA, Reese PP, Pruett TL, Hanson CS, O'Donoghue D, Tam-Tham H, Halimi JM, Shen JI, Kanellis J, Scandling JD, Howard K, Howell M, Cross N, Evangelidis N, Masson P, Oberbauer R, Fung S, Jesudason S, Knight S, Mandayam S, McDonald SP, Chadban S, Rajan T, Craig JC. Developing Consensus-Based Priority Outcome Domains for Trials in Kidney Transplantation: A Multinational Delphi Survey With Patients, Caregivers, and Health Professionals. Transplantation. 2017 Aug;101(8):1875-1886. doi: 10.1097/TP.0000000000001776.

Reference Type BACKGROUND
PMID: 28738403 (View on PubMed)

Tong A, Gill J, Budde K, Marson L, Reese PP, Rosenbloom D, Rostaing L, Wong G, Josephson MA, Pruett TL, Warrens AN, Craig JC, Sautenet B, Evangelidis N, Ralph AF, Hanson CS, Shen JI, Howard K, Meyer K, Perrone RD, Weiner DE, Fung S, Ma MKM, Rose C, Ryan J, Chen LX, Howell M, Larkins N, Kim S, Thangaraju S, Ju A, Chapman JR; SONG-Tx Investigators. Toward Establishing Core Outcome Domains For Trials in Kidney Transplantation: Report of the Standardized Outcomes in Nephrology-Kidney Transplantation Consensus Workshops. Transplantation. 2017 Aug;101(8):1887-1896. doi: 10.1097/TP.0000000000001774.

Reference Type BACKGROUND
PMID: 28737661 (View on PubMed)

Tong A, Sautenet B, Poggio ED, Lentine KL, Oberbauer R, Mannon R, Murphy B, Padilla B, Chow KM, Marson L, Chadban S, Craig JC, Ju A, Manera KE, Hanson CS, Josephson MA, Knoll G; SONG-Tx Graft Health Workshop Investigators. Establishing a Core Outcome Measure for Graft Health: A Standardized Outcomes in Nephrology-Kidney Transplantation (SONG-Tx) Consensus Workshop Report. Transplantation. 2018 Aug;102(8):1358-1366. doi: 10.1097/TP.0000000000002125.

Reference Type BACKGROUND
PMID: 29470347 (View on PubMed)

Ju A, Josephson MA, Butt Z, Jowsey-Gregoire S, Tan J, Taylor Q, Fowler K, Dobbels F, Caskey F, Jha V, Locke J, Knoll G, Ahn C, Hanson CS, Sautenet B, Manera K, Craig JC, Howell M, Rutherford C, Tong A, Harden P, Hawley C, Holdaas H, Israni A, Jesse M, Kane B, Kanellis J, Kiberd B, Kim J, Larsen C, Leichtman A, Lentine K, Malone A, Mannon R, Oberbauer R, Patzer R, Peipert JD, Phan HA, Poggio E, Reed R, Scandling J, Tang I, Watson C, Contrares D, Contreras P, Cross D, Juodvalkis E, Koide D, Koide J, Kozarewicz A, Kozarewicz L, Kozarewicz R, Koritala A, Lisiecki E, Lipuma C, Lyman M, Mueller R, Mueller G, Noble L, Nolan N, Nolan S, Thomas J, Urbancyzk L, Zerante J, Zerante S; SONG-Tx Life Participation Workshop Investigators; Health professionals (*includes 2 patients from the SONG-Tx Graft Health Expert Working Group); Patients and family members. Establishing a Core Outcome Measure for Life Participation: A Standardized Outcomes in Nephrology-kidney Transplantation Consensus Workshop Report. Transplantation. 2019 Jun;103(6):1199-1205. doi: 10.1097/TP.0000000000002476.

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Ju A, Chow BY, Ralph AF, Howell M, Josephson MA, Ahn C, Butt Z, Dobbels F, Fowler K, Jowsey-Gregoire S, Jha V, Locke JE, Tan JC, Taylor Q, Rutherford C, Craig JC, Tong A. Patient-reported outcome measures for life participation in kidney transplantation: A systematic review. Am J Transplant. 2019 Aug;19(8):2306-2317. doi: 10.1111/ajt.15267. Epub 2019 Feb 28.

Reference Type BACKGROUND
PMID: 30664327 (View on PubMed)

Other Identifiers

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GWCT051274

Identifier Type: -

Identifier Source: org_study_id

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