Transplant Trial Watch

Sirolimus versus mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study.

Girman, P., Lipár, K. et al. (2019).

American Journal of Transplantation [record in progress].

The aim of this study was to compare 5‐year patient and graft survival outcomes in type 1 diabetic kidney and pancreas recipients prospectively randomized for treatment either with sirolimus or mycophenolate mofetil (MMF) in combination with tacrolimus and early steroid withdrawal.

Patients were preoperatively randomized for prophylactic immunosuppressive treatment either with tacrolimus and sirolimus or tacrolimus and MMF. Methylprednisolone (250 mg) was administered before transplantation and following by 3 doses of 125 mg. Oral prednisone was initiated thereafter at 20 mg/day. The dose was gradually tapered before being completely withdrawn 6 weeks after transplantation.

238 type 1 diabetic recipients with end‐stage kidney disease due to undergo first‐time simultaneous pancreas and kidney transplantation.

The primary outcome of the study was to compare 5‐year pancreas graft survival. Pancreas graft failure was defined as death, graftectomy, retransplantation, or resumption of regular insulin therapy lasting more than 30 days (at any dose). Secondary outcomes were to assess patient survival, kidney survival, and wound healing time. Kidney graft failure was defined as death, retransplantation, resumption of regular dialysis, or graftectomy.

5 years

CET Conclusions
This was a single centre randomised controlled trial that was not blinded. There was a similar pancreas graft survival in both arms to 5 years, but out to 10 year follow up the sirolimus arm had a slight benefit when censored for death. 5-year rates of biopsy proven acute rejection were lower in the sirolimus arm. Incisional hernia rates were higher in the sirolimus arm (approximately 20% versus 12%) and rates of GI bleeding were significantly higher in the MMF arm. Given the early difficulties with wound healing, it may be more beneficial to convert to sirolimus after the first 3 months out from surgery. However, beyond this point there may be some slight benefits over MMF in terms of reduced acute rejection and improved death censored graft survival.

Jadad score

Data analysis
Strict intention-to-treat analysis

Allocation concealment

Trial registration - NCT 03582878

Funding source
Industry funded