Randomized Controlled Trial of Sirolimus Conversion in Cardiac Transplant Recipients With Renal Insufficiency
Zuckermann A, Keogh A, et al.American Journal of Transplantation, 12(9): 2487-2497, 2012.
Aims
To determine whether converting from a calcineurin inhibitor (CNI) to sirolimus therapy would confer beneficial effects on renal function in cardiac transplant recipients with mild to moderate renal dysfunction.
Interventions
Convert from a CNI (cyclosporine or tacrolimus) to sirolimus versus continue on CNI.
Participants
121 cardiac transplant recipients with mild to moderate renal impairment.
Outcomes
The primary endpoint was the change in calculated creatinine clearance at 52 weeks. Secondary endpoints were change in calculated creatinine at 4, 16, 24, 32 and 40 weeks. Other endpoints included change in serum creatinine level at 4, 16, 24, 32, 40 and 52 weeks, slope of creatinine clearance between 0-52 weeks, patient survival, incidence of biopsy confirmed acute rejection and antibody use for treatment of acute rejection. Safety assessments included adverse events, withdrawals, concomitant medications, vital signs, electrocardiography and incidence of major adverse cardiac events.
Follow-up
52 weeks
CET Conclusions
In this multicentre trial, patients with a heart transplant and renal dysfunction between 1 and 8 years after transplant were randomised to switch from CNI therapy to sirolimus or continue on CNI. The analysis showed that there was a modest improvement in calculated creatinine clearance in the patients who had switched to sirolimus but there was a little more acute rejection in the sirolimus group and a very much higher treatment discontinuation rate due to adverse events in the sirolimus group. Thus although conversion to sirolimus from CNI therapy improved renal function, this has to be weighed against the increased risk of acute rejection and the need to discontinue sirolimus because of a high rate of adverse events.
Data analysis
Modified intention-to-treat analysis
Trial registration
NCT00098007 (ClinicalTrials.gov)