Immunosuppressants for Kidney Transplant

Overseen By Gurvir Thind

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Must be taking: Tacrolimus, Cyclosporine

Disqualifiers: Extra-renal transplant, Active infection, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

96 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. However, it focuses on whether continuing immunosuppressants after a failed kidney transplant is beneficial, so you might need to stay on these medications if you are already taking them.

What data supports the effectiveness of immunosuppressant drugs for preventing allosensitization in kidney transplant patients?

Research shows that immunosuppressant drugs like mycophenolate mofetil, tacrolimus, and sirolimus have significantly reduced acute rejection rates in kidney transplant patients, which suggests they may help in preventing allosensitization (the immune system's response to foreign tissue). These drugs have improved short-term graft survival and decreased early mortality by reducing rejection episodes. ^{1 2 3 4 5}

Is the use of immunosuppressants for kidney transplants generally safe?

Immunosuppressants used in kidney transplants can have side effects like increased cardiovascular risk and kidney damage, but strategies to minimize these effects are being developed. Studies show that while these drugs are effective in preventing rejection, they can also lead to other health issues, so careful management is important. ^{6 7 8 9 10}

How does the drug for preventing allosensitization in kidney transplant patients differ from other treatments?

This treatment is unique because it aims to prevent allosensitization (the immune system's response to foreign tissue) by potentially minimizing the use of calcineurin inhibitors and corticosteroids, which are known for their toxicity. It may involve novel agents like belatacept or ASKP1240, which are designed to reduce side effects while maintaining effective immunosuppression. ^{1 3 5 10 11}

What is the purpose of this trial?

Kidney transplant is often the best treatment for people with kidney failure, but transplanted kidneys don't always last a lifetime. Many transplanted kidneys fail within 12 years, leaving patients needing dialysis or another transplant. One major issue is something called "allosensitization," which happens when the immune system attacks the donated kidney due to foreign markers on the kidney. This makes it harder to match a patient with another donor kidney in the future. To try to prevent this, patients are given immunosuppressants (drugs that weaken the immune system) after a transplant to stop the immune system from attacking the new kidney. However, after a kidney transplant fails and patients return to dialysis, there's no clear evidence that continuing immunosuppressants helps prevent allosensitization. Plus, these drugs have serious risks, including infections, heart disease, and even cancer. The PART study is a pilot study designed to explore whether continuing immunosuppression after a failed transplant for two years (instead of stopping after six months) can lower the risk of allosensitization and whether it is safe to do so. This pilot will also gather data that will be used for a larger trial in the future. The study will be done at 12 different research centers, and around 96 patients will be enrolled in the pilot trial. The ultimate goal is to better understand if continuing immunosuppressants after transplant failure can make a difference, and whether it's safe enough to proceed to a larger, more definitive trial.

Eligibility Criteria

The PART study is for patients who have had a kidney transplant fail and are now back on dialysis. It's to see if staying on immune-weakening drugs longer can prevent the body from rejecting future transplants. Participants must be adults who've recently had their first kidney transplant fail.

Inclusion Criteria

I am 19 or older, my first kidney transplant failed, and I am planning to start dialysis.

Exclusion Criteria

I am not taking tacrolimus or cyclosporine after my transplant failed.

I do not have an infection or another cancer that stops me from continuing my current treatment.

I don't have saved samples for transplant matching tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either continue immunosuppressive therapy for 24 months or withdraw after 6 months post dialysis initiation

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for adverse events and sensitization levels

24 months

Treatment Details

Interventions

• Prevention of Allosensitization

Trial Overview This pilot trial tests whether continuing immunosuppressants for two years after a failed kidney transplant reduces allosensitization, compared to stopping at six months. The safety of prolonged use will also be assessed across 12 research centers with about 96 participants.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

Patients will withdraw from immunosuppressant after 6 months post dialysis initiation

Group II: Arm 2 Active Control 1 Intervention

Patients will withdraw from immunosuppressant after 24 months post dialysis initiation

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

Contemporary immunosuppressive regimens for renal transplantation have significantly reduced acute rejection rates, but challenges like chronic allograft injury and adverse events remain, highlighting the need for improved therapies.

Investigational agents such as ASKP1240, a fully-human anti-CD40 monoclonal antibody, and alternatives to calcineurin inhibitors like belatacept and voclosporin are being explored to enhance graft outcomes while minimizing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel immunosuppressive agents in kidney transplantation. Hardinger, KL., Brennan, DC.[2021]

In a systematic review of 233 randomized controlled trials on kidney transplant immunosuppression, only 69% reported adverse events (AEs), and many did not adequately define or measure the severity of these events, raising concerns about the reliability of the data for clinical decision-making.

Trials that reported AEs were more likely to be industry-funded, multicenter, and have shorter follow-up periods, suggesting potential biases in the reporting of adverse effects that could impact patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Completeness of reporting of adverse events in trials of maintenance immunosuppression in kidney transplantation: a systematic review. Howell, M., Yeo, R., Tong, A., et al.[2022]

References

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

Outcomes in kidney transplantation. [2022]

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

Recent advances in immunosuppressive therapy for renal transplantation. [2021]

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

Novel immunosuppressive agents in kidney transplantation. [2021]

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

Immunosuppressive strategies to improve outcomes of kidney transplantation. [2021]

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

A decade of progress in kidney transplantation. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Completeness of reporting of adverse events in trials of maintenance immunosuppression in kidney transplantation: a systematic review. [2022]

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

Regimen of tacrolimus-based immunosuppression with basiliximab, mycophenolate mofetil, and low-dose steroid reduces acute rejection in kidney transplants. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The need for minimization strategies: current problems of immunosuppression. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Tacrolimus and cyclosporine efficacy in high-risk kidney transplantation. European Multicentre Tacrolimus (FK506) Renal Study Group. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Immunosuppression and Kidney Transplantation. [2022]

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

Kidney transplantation: the ideal immunosuppression regimen. [2021]