Steroids for Kidney Transplant Rejection

Recruiting at 25 trial locations

Overseen By Angela Rejuso, BMSc(Hons)

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Sydney

Must not be taking: Immunomodulatory agents

Disqualifiers: Mixed rejection, Active ABMR, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 3 days for IV treatment, followed by 7 days of oral prednisone

540 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain immunomodulatory agents (drugs that affect the immune system) or are enrolled in other drug trials.

What data supports the effectiveness of the drug Methylprednisolone for kidney transplant rejection?

Research shows that higher doses of Methylprednisolone can reduce the number and severity of rejection episodes early after kidney transplantation. However, it does not significantly improve overall graft survival compared to other steroids like Prednisone. ^{1 2 3 4 5}

Is the use of steroids like methylprednisolone and prednisone safe for kidney transplant patients?

Steroids like methylprednisolone and prednisone are generally used in kidney transplants, but they can increase the risk of infections like bacterial sepsis (a severe infection) and may cause weight gain. Some studies suggest that high doses of methylprednisolone might slightly increase the risk of complications and mortality. ^{1 2 3 6 7}

How does the drug Methylprednisolone, Prednisone differ from other treatments for kidney transplant rejection?

Methylprednisolone and Prednisone are steroids used to prevent and treat kidney transplant rejection by suppressing the immune system. They are unique because they can be administered in varying doses to modify the severity of rejection episodes, and they are often used in combination with other immunosuppressive drugs. Unlike some treatments, they are effective in reversing rejection but are not always necessary at the moment of transplantation if other immunosuppressive agents like cyclosporine are used. ^{1 2 3 7 8}

What is the purpose of this trial?

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.

Research Team

Julie Ho, FRCPC

Principal Investigator

University of Manitoba

Germaine Wong, PhD, FRACP

Principal Investigator

University of Sydney

Eligibility Criteria

The TACKLE-IT Trial is for patients who have had a kidney or kidney-pancreas transplant and are experiencing organ rejection, specifically Acute T cell mediated rejection (TCMR). The trial aims to find the right steroid dose to treat this condition.

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

My ethnicity or gender does not affect my eligibility.

Exclusion Criteria

I have ongoing kidney disease, like repeated kidney inflammation or a virus affecting my kidneys.

I do not have any active infections or cancers that would prevent me from receiving treatments to boost my immune system.

Unable to adhere to the study protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high or low dose IV methylprednisolone and oral prednisone to treat acute T cell mediated rejection

3 days for IV treatment, followed by 7 days of oral prednisone

Daily visits for IV treatment, followed by weekly monitoring

Follow-up

Participants are monitored for safety, effectiveness, and various outcomes such as infections, quality of life, and kidney function

48 weeks

Visits at 12, 24, and 48 weeks post-randomization

Long-term monitoring

Participants are monitored for long-term outcomes such as chronic fibrosis, cancer, and all-cause death

48 weeks

Treatment Details

Interventions

• Methylprednisolone
• Prednisone

Trial Overview This study tests different doses of steroids, Methylprednisolone and Prednisone, to determine the most effective amount that can manage acute TCMR in transplant recipients without causing significant side effects.

Participant Groups

Group I: Lower dose IV methylprednisolone x Lower dose oral prednisone Experimental Treatment 2 Interventions

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 II: Lower dose IV methylprednisolone x Higher dose oral prednisone Experimental Treatment 2 Interventions

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 III: Higher dose IV methylprednisolone x lower dose oral prednisone Active Control 2 Interventions

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 IV: Higher dose IV methylprednisolone x higher dose oral prednisone Active Control 2 Interventions

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.

Methylprednisolone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in European Union as Depo-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in Canada as Solu-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Who Is Running the Clinical Trial?

University of Sydney

Lead Sponsor

Trials

208

Recruited

417,000+

University of Manitoba

Collaborator

Trials

628

Recruited

209,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

A prospective study of methylprednisolone and prednisone as immunosuppressive agents in clinical renal transplantation. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Comparison of two different immunosuppressive dosages of methylprednisolone in clinical renal transplantation. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Steroid avoidance regimens: a comparison of outcomes with maintenance steroids versus continued steroid avoidance in recipients having an acute rejection episode. [2023]

4. Italy pubmed.ncbi.nlm.nih.gov

[The use of methylprednisolone in the therapy of renal transplants from cadavers]. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Oral versus intravenous high-dose steroid treatment of renal allograft rejection. The big shot or not? [2019]

6. United States pubmed.ncbi.nlm.nih.gov

High dose (bolus) intravenous methylprednisolone at the time of kidney homotransplantation. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Steroid sensitivity of chronic uraemic and renal transplant patients measured by the antibody dependent cellular cytotoxicity reaction. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Effects of steroids in combination with other pharmacologic immunosuppressive agents. [2013]