Study Evaluating Conversion From Tacrolimus to Sirolimus in Stable Kidney Transplant Recipients Receiving Myfortic (MYFIIRP)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study to Evaluate the Safety and Efficacy of Mycophenolate Sodium (Myfortic®) in Combination With Sirolimus (Rapamune®) in Stable Renal Allograft Recipients|
- Renal allograft function [ Time Frame: six months ] [ Designated as safety issue: No ]
- Control of hypertension, diabetes and hyperlipidemia; incidence of new onset diabetes after transplantation (NODAT), acute rejection, infectious complications and severe adverse events; and patient and graft survival. [ Time Frame: six months ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2007|
|Study Completion Date:||November 2010|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
All subjects who enroll in this study will be converted from their calcineurin inhibitor to sirolimus.
Oral tablet(s) taken daily for 6 months; dose will be based on serum trough levels.
One-year graft survival after renal transplantation dramatically improved with the addition of calcineurin inhibitors (tacrolimus or cyclosporine) to maintenance immunosuppression regimens. Much of this improvement in early graft survival has been attributed to the efficacy of the calcineurin inhibitors in preventing early acute rejection episodes. However, long-term graft survival has not improved to as great of a magnitude as the improvements in short-term survival. In addition, research shows progressive decline in kidney function throughout the years post-transplantation. Clinical research now focuses on improving long term graft survival while maintaining long-term kidney function.
The leading cause of graft loss has been attributed to chronic allograft nephropathy (CAN). Risk factors for CAN include: prolonged ischemia time, delayed graft function, acute rejection episodes and calcineurin inhibitor nephrotoxicity (CIN). CIN has been identified as the most common identifiable contributor to CAN and the chief cause of late histologic injury and ongoing decline in renal function. At 10 years post-transplant, CIN has been found to be universally prevalent.
Calcineurin inhibitor minimization and elimination studies have sought to improve long-term allograft function by minimizing exposure to these nephrotoxic agents. Studies have demonstrated that early withdrawal of cyclosporine from a cyclosporine, sirolimus and steroid immunosuppression regimen at 3 months post-transplant improved renal function and graft survival at 48 months post-transplant. Other studies have demonstrated diminished prevalence of CAN at 2 years post-transplant in those patients maintained on sirolimus as compared with cyclosporine. Kidney function was also significantly improved with lower serum creatinine and higher GFR in the sirolimus maintenance group.
Sirolimus is a macrolide antibiotic immunosuppressive agent that exerts its mechanism of action by inhibiting the mTOR signaling cascade. In clinical trials, sirolimus was found to lack nephrotoxic effects when compared to cyclosporine. In kidney transplantation, multiple studies have demonstrated safety and efficacy of sirolimus in calcineurin inhibitor avoidance and withdrawal protocols.
Myfortic® (mycophenolate acid) is an enteric coated formulation of mycophenolic acid (MPA) approved for the prevention of rejection in kidney transplant recipients in combination with cyclosporine and corticosteroids. Myfortic® has no documented nephrotoxic effects. Mycophenolate mofetil (MMF), a prodrug of MPA also does not demonstrate nephrotoxic effects. Early studies have demonstrated therapeutic equivalence between Myfortic® and MMF both in de novo renal transplants and in conversion studies where MMF is converted to Myfortic at least 6 months after renal transplantation. Thus, studies demonstrating safety and efficacy of MMF with sirolimus in calcineurin inhibitor withdrawal protocols should also hold true using Myfortic® in such regimen.
This study will assess the safety and efficacy of Myfortic® when used in a simultaneous sirolimus conversion and calcineurin inhibitor withdrawal regimen in stable renal transplant recipients. Study subjects will receive immunosuppression consisting of Myfortic®, tacrolimus and corticosteroids (prednisone) starting the day of transplant. Conversion from tacrolimus (Prograf) to sirolimus (Rapamune) will occur between 90 and 180 days post cadaver-donor or living-donor renal transplant. All participants will be converted from tacrolimus to sirolimus and remain on Myfortic® and their current corticosteroid taper.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00713284
|United States, California|
|California Pacific Medical Center; Barry S. Levin, MD Department of Transplantation|
|San Francisco, California, United States, 94115|
|Principal Investigator:||V. Ram Peddi, MD||California Pacific Medical Center|