Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study

Acute rejection episodes after renal transplantation are an important clinical challenge, despite use of multidrug immunosuppressive regimens. We did a prospective, multicentre, randomised, double-blind trial to investigate the impact of the addition of sirolimus, compared with azathioprine, to a ciclosporin and prednisone regimen. 719 recipients of primary HLA-mismatched cadaveric or living-donor renal allografts who displayed initial graft function were randomly assigned, after transplantation, sirolimus 2 mg daily (n=284) or 5 mg daily (n=274), or azathioprine (n=161). We assessed the primary composite endpoint of efficacy failure, occurrence of biopsy-confirmed acute rejection episodes, graft loss, or death, and various secondary endpoints that characterise these episodes at 6 months and 12 months. Analyses were done by intention to treat. The rate of efficacy failure at 6 months was lower in the two sirolimus groups (2 mg 18·7%, p=0·002; 5 mg 16·8%, p