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

University of Sydney

Status and phase: Not yet enrolling; Phase 3

Conditions: Rejection; Transplant, Kidney; Rejection; Transplant, Pancreas

Treatments: Drug: Methylprednisolone; Drug: Prednisone

Study type: Interventional

Funder types: Other

Identifiers

NCT06474273

GWCT051274

Details and patient eligibility

About

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.

Full 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?'

Enrollment: 540 estimated patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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540 participants in 4 patient groups

Lower dose IV methylprednisolone x Lower dose oral prednisone

Experimental group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Methylprednisolone

Lower dose IV methylprednisolone x Higher dose oral prednisone

Experimental group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Methylprednisolone

Higher dose IV methylprednisolone x lower dose oral prednisone

Active Comparator group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Methylprednisolone

Higher dose IV methylprednisolone x higher dose oral prednisone

Active Comparator group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Methylprednisolone