80 Participants Needed

Simplified Immunosuppression for Kidney Transplant

(SIMPLE Trial)

MR
Overseen ByMelissa Ramos, BSN
Age: 18+
Sex: Any
Trial Phase: Phase 4
Sponsor: University of Southern California
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if the combination of once-daily tacrolimus extended-release (EnvarsusXR) and Azathioprine is non inferior with respect to the composite outcome of acute rejection, graft and patient survival as compared to a combination of twice-daily immediate release tacrolimus and mycophenolate mofetil/mycophenolic acid.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since the study involves specific immunosuppressive drugs, you may need to adjust your current medication regimen. Please consult with the study team for guidance.

What data supports the idea that Simplified Immunosuppression for Kidney Transplant is an effective treatment?

The available research shows that mycophenolate mofetil (MMF), a drug used in Simplified Immunosuppression for Kidney Transplant, is associated with a lower rate of acute rejection compared to azathioprine (AZA). Specifically, MMF results in a 50% lower incidence of acute rejection. Additionally, some studies suggest better long-term kidney survival with MMF compared to AZA, although results vary across different studies. This indicates that MMF may be more effective in preventing the body from rejecting the transplanted kidney.12345

What safety data is available for immunosuppressive treatments in kidney transplants?

The safety of mycophenolate mofetil (MMF) compared to azathioprine (Aza) in kidney transplantation has been evaluated in several studies. A systematic review focused on their side effects, and another study investigated the safety of converting from MMF to Aza in stable renal transplant patients. These studies provide evidence-based insights into the safety profiles of these immunosuppressive treatments.23456

Is the drug combination of Azathioprine, Methylprednisolone, prednisone, Mycophenolate mofetil (MMF) or Mycophenolic acid (MPA), Once-daily envarsus XR, and Tacrolimus a promising treatment for kidney transplant?

Yes, the drug combination is promising for kidney transplant. Studies show that using Mycophenolate mofetil (MMF) with Tacrolimus leads to better outcomes, like fewer cases of the body rejecting the new kidney, compared to using Azathioprine. This combination is effective and safe for kidney transplant patients.23457

Research Team

SV

Santhi Voora, MD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for adults aged 18-85 who have recently received a kidney transplant. They should have a cold ischemia time of less than 24 hours if there's a significant mismatch in donor and recipient tissue types, or more than 24 hours for fewer mismatches. Their pre-transplant antibody levels must be low (≤20%).

Inclusion Criteria

I am between 18 and 85 years old and have received a new kidney transplant.
Your cPRA test results must be less than 20% before getting a transplant.
My organ transplant matches well if cold time is under 24 hours for 3-6 mismatches, and over 24 hours for less than 3 mismatches.

Treatment Details

Interventions

  • Azathioprine
  • Methylprednisolone, prednisone
  • Mycophenolate mofetil (MMF) or Mycophenolic acid (MPA)
  • Once-daily envarsus XR
  • Tacrolimus
Trial OverviewThe study tests whether taking EnvarsusXR (a once-daily tacrolimus) with Azathioprine works as well as the standard treatment of twice-daily Tacrolimus with Mycophenolate mofetil/acid to prevent organ rejection without affecting patient survival.
Participant Groups
2Treatment groups
Active Control
Group I: Twice-daily RegimenActive Control4 Interventions
Twice-daily regimen of immediate release tacrolimus, mycophenolate mofetil (MMF)/mycophenolic acid (MPA) plus daily methylprednisolone or prednisone.
Group II: Once-daily RegimenActive Control4 Interventions
Once-daily regimen of Envarsus, azathioprine plus methylprednisolone or prednisone.

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

🇪🇺
Approved in European Union as Imuran for:
  • Prevention of rejection in organ transplantation
  • Treatment of autoimmune diseases such as rheumatoid arthritis
🇺🇸
Approved in United States as Imuran for:
  • Prevention of rejection in organ transplantation
  • Treatment of rheumatoid arthritis
🇨🇦
Approved in Canada as Imuran for:
  • Prevention of rejection in organ transplantation
  • Treatment of rheumatoid arthritis

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials
956
Recruited
1,609,000+

Veloxis Pharmaceuticals

Industry Sponsor

Trials
43
Recruited
3,200+

Findings from Research

In a retrospective study comparing mycophenolate mofetil (MMF) and azathioprine (AZA) in renal transplantation, no significant difference in long-term graft survival was found between the two immunosuppressive regimens, despite MMF showing a lower incidence of acute rejection shortly after transplantation.
The study suggests that early benefits of MMF in reducing acute rejection may not lead to improved long-term outcomes, potentially due to various non-immunological factors affecting graft survival.
Comparison of long-term actual renal allograft survival in mycophenolate mofetil and azathioprine-based triple drug immunosuppression protocols.Attallah, N., Goggins, M., Nori, U., et al.[2016]
Mycophenolate acid (MMF) at a dosage of 2 g/day is more effective than azathioprine (AZA) in improving graft and long-term patient survival rates after renal transplantation, based on a review of 23 randomized controlled trials.
Both MMF dosages (2 g/day and 3 g/day) significantly reduce the incidence of biopsy-proven rejection compared to AZA, with the 2 g/day dosage being more acceptable for patients.
Efficacy of mycophenolate mofetil versus azathioprine after renal transplantation: a systematic review.Wang, K., Zhang, H., Li, Y., et al.[2018]
In a study of 87 stable renal transplant patients, switching from mycophenolate mofetil (MMF) to Azathioprine (AzA) after 6 months did not negatively impact graft survival or increase acute rejection rates over a 12-month follow-up.
While the conversion to AzA was deemed safe and necessary in certain economic contexts, it was associated with a higher incidence of reversible side effects like liver lesions and leukocytopenia compared to those who continued on MMF.
[Necessity and safety of conversion from mycophenolate mofetil to AzA thioprine after renal transplantation].Lu, JS., Xiao, XR., Ao, JH., et al.[2016]

References

Comparison of long-term actual renal allograft survival in mycophenolate mofetil and azathioprine-based triple drug immunosuppression protocols. [2016]
Efficacy of mycophenolate mofetil versus azathioprine after renal transplantation: a systematic review. [2018]
[Necessity and safety of conversion from mycophenolate mofetil to AzA thioprine after renal transplantation]. [2016]
Mycophenolate versus azathioprine for kidney transplantation: a 15-year follow-up of a randomized trial. [2016]
A Study of the Pharmacokinetic Comparison between the Generic and Original Form of Mycophenolate Mofetil Among Thai Renal Transplant Patients. [2019]
Safety of mycophenolate mofetil versus azathioprine in renal transplantation: a systematic review. [2018]
Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years. [2022]