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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06474273




Registration number
NCT06474273
Ethics application status
Date submitted
19/06/2024
Date registered
25/06/2024
Date last updated
25/06/2024

Titles & IDs
Public title
TACKLE-IT Trial - Treat Acute T Cell Rejection With Evidence and Confidence in Kidney Transplant Recipients
Scientific title
A Multicenter Randomized Controlled Trial to Treat Acute t Cell Mediated Rejection in Kidney and Kidney-pancreas Transplant Recipients
Secondary ID [1] 0 0
GWCT051274
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rejection; Transplant, Kidney 0 0
Rejection; Transplant, Pancreas 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Methylprednisolone
Treatment: Drugs - Prednisone

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 for those \< 18 years ) vs higher dose (50mg daily x 7 days, or or 30mg/m2 for those \< 18 years) oral prednisone augmentation.

Experimental: Lower dose IV methylprednisolone x Higher 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 higher dose (50mg daily x 7 days, or or 30mg/m2 for those \< 18 years) oral prednisone augmentation.

Active comparator: Higher dose IV methylprednisolone x lower dose oral prednisone - Higher dose IV MP (500 mg daily x 3 days 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.

Active comparator: Higher dose IV methylprednisolone x higher dose oral prednisone - Higher dose IV MP (500 mg daily x 3 days 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.


Treatment: Drugs: Methylprednisolone
IV Methylprednisolone

Treatment: Drugs: Prednisone
Oral prednisone augmentation
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Histological resolution of biopsy-proven acute rejection
Timepoint [1] 0 0
12 weeks post-randomization
Primary outcome [2] 0 0
Improvement in allograft function
Timepoint [2] 0 0
12 weeks post-randomization
Primary outcome [3] 0 0
Avoidance of rescue therapies within 12 weeks post-randomisation to achieve histological resolution and/or improvement in allograft function
Timepoint [3] 0 0
12 weeks post-randomization
Secondary outcome [1] 0 0
Estimated glomerular filtration rate (eGFR)
Timepoint [1] 0 0
At 12, 24 and 48 weeks post-randomization
Secondary outcome [2] 0 0
All cause death and death-censored graft loss
Timepoint [2] 0 0
At 12 weeks post-randomization
Secondary outcome [3] 0 0
Urine albumin: creatinine ratios
Timepoint [3] 0 0
At 12, 24 and 48 weeks post-randomization
Secondary outcome [4] 0 0
Trajectories of serum creatinine changes
Timepoint [4] 0 0
From randomization to 48 weeks
Secondary outcome [5] 0 0
Development of acute antibody mediated rejection (ABMR) and mixed rejection (concomitant ABMR + TCMR)
Timepoint [5] 0 0
48 weeks post randomization
Secondary outcome [6] 0 0
Development of chronic fibrosis in the allograft
Timepoint [6] 0 0
Baseline to 12 weeks post-randomisation
Secondary outcome [7] 0 0
Infections (requiring antimicrobials and hospitalisation)
Timepoint [7] 0 0
Anytime from randomization to 48 weeks
Secondary outcome [8] 0 0
Quality of life (QoL)
Timepoint [8] 0 0
At randomization, 12 weeks post-randomization, 24 weeks post-randomization, and 48 weeks post-randomization
Secondary outcome [9] 0 0
Infections (all types)
Timepoint [9] 0 0
Anytime from randomization to 48 weeks
Secondary outcome [10] 0 0
Cancer
Timepoint [10] 0 0
Anytime from randomization to 48 weeks

Eligibility
Key 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).
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.
* Higher grade acute TCMR, =Banff 2A.
* 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/12/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2029
Actual
Sample size
Target
540
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Hospital - Lambton
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 0 0
The Sydney Children's Hospital Network - Westmead
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [9] 0 0
Royal Children's Hospital Melbourne - Parkville
Recruitment hospital [10] 0 0
Royal Perth Children's hospital - Nedlands
Recruitment hospital [11] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [12] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2305 - Lambton
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
2014 - South Brisbane
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment postcode(s) [8] 0 0
3052 - Parkville
Recruitment postcode(s) [9] 0 0
6009 - Nedlands
Recruitment postcode(s) [10] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
Manitoba
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec
Country [5] 0 0
Canada
State/province [5] 0 0
Saskatchewan
Country [6] 0 0
New Zealand
State/province [6] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of Manitoba
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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's 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.
Trial website
https://clinicaltrials.gov/study/NCT06474273
Trial related presentations / 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Germaine Wong, PhD, FRACP
Address 0 0
University of Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Chandana Guha, MEcon
Address 0 0
Country 0 0
Phone 0 0
9845 1229
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06474273