Steroids for Kidney Transplant Rejection

Not yet recruiting at 27 trial locations
CG
AR
Overseen ByAngela Rejuso, BMSc(Hons)
Age: Any Age
Sex: Any
Trial Phase: Phase 3
Sponsor: University of Sydney
No Placebo GroupAll 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 DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal steroid dose for treating rejection in patients who have received a kidney or kidney-pancreas transplant. The body sometimes rejects these new organs, leading to issues that could impair their function. Researchers will test various doses of two steroids, methylprednisolone (also known as Medrol, Depo-Medrol, or Solu-Medrol) and prednisone, to identify the most effective option. Individuals who have undergone a kidney transplant and are experiencing acute T cell mediated rejection (TCMR) may be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both methylprednisolone and prednisone help manage organ rejection after kidney transplants. Studies have found that lower doses of methylprednisolone, such as 250 mg, can be as effective as higher doses, like 1,000 mg, for treating sudden rejection in kidney transplants. This suggests that lower doses might be safer and cause fewer side effects while maintaining effectiveness.

Prednisone is often used regularly to prevent rejection. Research indicates that ongoing use of steroids like prednisone can cause side effects, but they are crucial for preventing organ rejection. The goal is to find the right dose that prevents rejection with the least side effects.

This trial tests different combinations of low and high doses of these steroids to identify the safest and most effective dose. The trial aims to reduce risks like infections and weight gain, which can occur with high doses of steroids. Although methylprednisolone and prednisone are usually well-tolerated, high doses can lead to issues like diabetes or bone problems. This trial is important for finding a safer dose that remains effective.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore varying doses of methylprednisolone and prednisone to combat kidney transplant rejection. Unlike standard care that often uses a one-size-fits-all dosage, these treatments are tailored with both lower and higher dose combinations, potentially optimizing effectiveness while minimizing side effects. The ability to customize steroid doses could lead to more personalized care, improving outcomes for transplant patients by better managing immune responses. This approach seeks to fine-tune the balance between efficacy and patient tolerance, which is a significant step forward in transplant medicine.

What evidence suggests that this trial's treatments could be effective for kidney transplant rejection?

This trial will compare different dosing regimens of steroids to manage kidney transplant rejection. Research has shown that steroids like methylprednisolone and prednisone can help manage this condition. One study found that about 15% of kidney transplant patients who stopped taking prednisone early experienced at least one episode of acute rejection. This finding highlights the important role steroids play in preventing the body from rejecting a new kidney. However, the correct dose is crucial, as excessive amounts can cause side effects like heart problems and infections. Finding the right balance in steroid dosing is key to maintaining the new kidney's health without causing other health issues. Participants in this trial will receive varying doses of IV methylprednisolone and oral prednisone to determine the most effective and safe dosing strategy.678910

Who Is on the Research Team?

JH

Julie Ho, FRCPC

Principal Investigator

University of Manitoba

GW

Germaine Wong, PhD, FRACP

Principal Investigator

University of Sydney

Are You a Good Fit for This Trial?

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.
See 1 more

Exclusion Criteria

I do not have any active infections or cancers that would prevent me from receiving treatments to boost my immune system.
I have ongoing kidney disease, like repeated kidney inflammation or a virus affecting my kidneys.
Unable to adhere to the study protocol
See 8 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Active Control
Group I: Lower dose IV methylprednisolone x Lower dose oral prednisoneExperimental Treatment2 Interventions
Group II: Lower dose IV methylprednisolone x Higher dose oral prednisoneExperimental Treatment2 Interventions
Group III: Higher dose IV methylprednisolone x lower dose oral prednisoneActive Control2 Interventions
Group IV: Higher dose IV methylprednisolone x higher dose oral prednisoneActive Control2 Interventions

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

🇺🇸
Approved in United States as Medrol for:
🇪🇺
Approved in European Union as Depo-Medrol for:
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Approved in Canada as Solu-Medrol for:

Find a Clinic Near You

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+

Citations

Twenty‐Year Kidney Transplant Outcomes With ...There has been concern about long‐term outcomes of kidney transplant recipients treated with prednisone‐free maintenance immunosuppression.
Steroid Avoidance Regimens: A Comparison of Outcomes ...Roughly 15% of kidney transplant recipients on a rapid discontinuation of prednisone (RDP) protocol have ≥1 episode of acute rejection (AR).
Outcomes of Late Corticosteroid Withdrawal after Renal ...Although statistically not significant, our findings indicate that late corticosteroid withdrawal in kidney transplant patients is associated with 34% increase ...
The Outcome of Tapered Steroid Regimen When Used to ...Conclusion: When rapid steroid regimen was used to treat acute BCR after kidney transplant, only smaller number of patients showed response ...
Study Details | NCT00596947 | Prednisone Withdrawal ...The incidence and severity of rejection episodes per participant would have been identified by kidney transplant biopsy results read by a transplant pathologist ...
A Randomized Controlled Trial on Safety of Steroid Avoidance ...Steroid-based immunosuppression after transplantation increases the risk of post-transplant diabetes mellitus (PTDM), with adverse effects on patient and graft ...
A Randomized, Multicenter Study of Steroid Avoidance ...A multicenter, randomized trial showed that steroid withdrawal at 4 days posttransplant resulted in a similar incidence of rejection compared to standard ...
Balancing Steroid Exposure, Rejection Risk, and Infectious ...The most recent and comprehensive study on the safety and efficacy of early steroid withdrawal in kidney transplant recipients is the Harmony ...
versus Low-Dose Methylprednisolone for Acute Rejection ...We conclude that (1) 250 mg MP is as effective as 1,000 mg in reversing acute rejection in renal allografts; (2) 1,000 mg MP does not result in ...
Therapy in the Course of Kidney Graft Rejection ...In that research, methylprednisolone 500 mg was administered intravenously for three days, followed by oral prednisone 5 mg daily for more than four weeks.
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