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Published on: November 8, 2015
Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation
Richard Trompeter1, Guido Filler, Nicholas J A Webb
1Children's Hospital of Eastern Ontario, University of Ottawa, Canada.
Insights
Tacrolimus (Tac) significantly reduced acute rejection in pediatric renal transplant patients compared to cyclosporine (CyA) microemulsion. Tac demonstrated improved graft function and comparable safety, establishing its efficacy in this population.
Area of Science:
- Nephrology
- Immunology
- Pediatric Surgery
Background:
- Pediatric renal transplantation requires effective immunosuppression to prevent rejection.
- Tacrolimus (Tac) and cyclosporine (CyA) are commonly used immunosuppressants.
- Comparing the efficacy and safety of Tac versus microemulsion CyA in children is crucial for optimizing post-transplant outcomes.
Purpose of the Study:
- To compare the efficacy and safety of tacrolimus (Tac) with microemulsion cyclosporine (CyA) in pediatric patients undergoing renal transplantation.
- To evaluate the incidence and time to first acute rejection as the primary endpoint.
- To assess patient survival, graft loss, renal function, and adverse events.
Main Methods:
- A 6-month, randomized, prospective, open-label, parallel-group study was conducted across 18 European centers.
- 196 pediatric patients (<18 years) were randomized to receive either Tac or CyA microemulsion, with azathioprine and corticosteroids.
- Primary endpoint: incidence and time to first acute rejection. Secondary endpoints included graft survival, renal function (GFR), and safety assessments.
Main Results:
- Tacrolimus therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared to CyA (59.1%) (P=0.003).
- Biopsy-confirmed acute rejection was significantly lower with Tac (16.5%) versus CyA (39.8%) (P<0.001).
- Mean glomerular filtration rate at 1 year was significantly higher in the Tac group (62 ml/min/1.73 m²) than in the CyA group (56 ml/min/1.73 m²) (P=0.03). Patient survival and graft loss rates were comparable.
Conclusions:
- Tacrolimus is significantly more effective than microemulsion cyclosporine in preventing acute rejection in pediatric renal transplant recipients.
- The overall safety profiles of Tac and CyA microemulsion were comparable, with some differences in specific adverse events.
- Tacrolimus demonstrates superior efficacy and comparable safety, supporting its use in pediatric renal transplantation.
Abstract:
This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with the microemulsion formulation of cyclosporin (CyA) in children undergoing renal transplantation. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 years) were randomly assigned (1:1) to receive either Tac ( n=103) or CyA microemulsion ( n=93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection. Baseline characteristics were comparable between treatment groups. Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA therapy (59.1%) ( P=0.003). The incidence of corticosteroid-resistant rejection was also significantly lower in the Tac group compared with the CyA group (7.8% vs. 25.8%, P=0.001). The differences were also significant for biopsy-confirmed acute rejection (16.5% vs. 39.8%, P<0.001). At 1 year, patient survival was similar (96.1% vs. 96.6%), while 10 grafts were lost in the Tac group compared with 17 graft losses in the CyA group ( P=0.06). At 1 year, mean glomerular filtration rate (Schwartz estimate) was significantly higher in the Tac group (62+/-20 ml/min per 1.73 m(2), n=84) than in the CyA group (56+/-21 ml/min per 1.73 m(2), n=74, P=0.03). The most frequent adverse events during the first 6 months were hypertension (68.9% vs. 61.3%), hypomagnesemia (34.0% vs. 12.9%, P=0.001), and urinary tract infection (29.1% vs. 33.3%). Statistically significant differences ( P<0.05) were observed for diarrhea (13.6% vs. 3.2%), hypertrichosis (0.0% vs. 7.5%), flu syndrome (0.0% vs. 5.4%), and gum hyperplasia (0.0% vs. 5.4%). In previously non-diabetic children, the incidence of long-term (>30 days) insulin use was 3.0% (Tac) and 2.2% (CyA). Post-transplant lymphoproliferative disease was observed in 1 patient in the Tac group and 2 patients in the CyA group. In conclusion, Tac was significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population. The overall safety profiles of the two regimens were comparable.
