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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether continuing immunosuppressants, which reduce immune system activity, after a kidney transplant fails can prevent the immune system from attacking future donor kidneys. The study compares two groups: one stops the drugs six months after starting dialysis, and the other stops after 24 months. The goal is to determine if a longer duration of these drugs is beneficial and safe. Individuals whose first kidney transplant has failed and are starting dialysis are suitable candidates for this trial. As an unphased trial, it offers participants the chance to contribute to important research that could enhance future transplant outcomes.

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.

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

Research has shown that stopping immunosuppressants (drugs that weaken the immune system) after a kidney transplant can be safe, depending on timing and individual circumstances. Some studies indicate that stopping these drugs early can be very safe. For instance, patients who discontinued steroids (a type of immunosuppressant) soon after their transplant experienced good long-term safety results.

One study found that most people who stopped taking immunosuppressants did well, but a few had to restart the medication because their immune system began attacking the kidney. This suggests that while some individuals can safely stop taking the drugs, others might need to continue to avoid complications.

Overall, deciding whether to stop or continue taking immunosuppressants requires careful consideration of possible risks like infections or other serious side effects. The current trial investigates whether continuing these drugs for a longer period after a failed transplant might prevent problems without causing harm. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores different strategies to safely reduce reliance on immunosuppressants for kidney transplant patients. Current treatments typically require lifelong use of these drugs to prevent organ rejection, which can lead to serious side effects. This trial investigates the possibility of withdrawing immunosuppressants after 6 to 24 months post-dialysis initiation, potentially minimizing side effects while maintaining transplant health. By finding the optimal timeframe for reducing immunosuppressant use, the trial aims to improve the quality of life for kidney transplant recipients.

What evidence suggests that continuing immunosuppressants after transplant failure might be effective for preventing allosensitization?

This trial will compare two approaches to withdrawing immunosuppressants after a failed kidney transplant. Research has shown that stopping medications that suppress the immune system can make the body more sensitive to future donor kidneys, increasing the risk of the immune system attacking a new kidney. One study found that stopping these medications increases the risk of this immune reaction. Another study showed that continuing these medications might help prevent this problem, improving the chances of a successful future transplant. However, these drugs can cause serious side effects, such as infections and heart problems. Therefore, weighing the benefits against the possible risks is important. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

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 don't have saved samples for transplant matching tests.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12520163/

Twenty‐Year Kidney Transplant Outcomes With ... The estimated 20‐year graft survival for RDP was 32.4% and for MP was 30.8%; the estimated 20‐year death‐censored graft survival for RDP was ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1600613524002028

Immunosuppression withdrawal in living-donor renal ... Six of the 10 subjects successfully completed ISW. Of these 6 subjects, 4 restarted immunosuppressive medications due to acute rejection or recurrent disease, 1 ...

3. gavinpublishers.com gavinpublishers.com/article/view/evaluating-the-impact-of-steroid-withdrawal-on-outcomes-in-kidney-transplant-recipients-a-systematic-review-and-meta-analysis

Evaluating the Impact of Steroid Withdrawal on Outcomes ... Numerous studies have explored SW's efficacy in kidney transplant recipients, but outcomes have been mixed [16-18]. Certain investigations suggest increased ...

4. frontierspartnerships.org frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2023.11802/full

Impact of Infection-Related Immunosuppressant Reduction on ... The objective of this study is to identify the association between ISR due to infection at different phases after transplantation and the risk of rejection.

5. frontiersin.org frontiersin.org/journals/nephrology/articles/10.3389/fneph.2023.1163581/full

Continuation of immunosuppression vs. ... Withdrawal of immunosuppression in a re-transplant candidate can result in allosensitization and markedly reduce the chances of a repeat transplant.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3960772/

Three-Year Outcomes in Kidney Transplant Patients ... The primary efficacy endpoint of treatment failure (clinical biopsy-proven acute rejection (BPAR) graft loss, death, or loss to follow-up) occurred in 21.4% (95 ...

7. academic.oup.com academic.oup.com/ndt/article/39/1/141/7216509

Excellent efficacy and beneficial safety during observational 5 ... What was known: Short-term results of rapid steroid withdrawal (RSWD) 1 year after renal transplantation demonstrate excellent efficacy and ...

8. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2775940

Early Corticosteroid Cessation vs Long-term ... This study demonstrates the long-term safety of corticosteroid withdrawal in kidney transplant recipients after a median follow-up of 15.8 ...