Basiliximab and rabbit anti-thyrnocyte globulin for prophylaxis of acute rejection after heart transplantation: A non-inferiority trial

Background: Induction of immunosuppression with antibodies after heart transplantation decreases early acute rejection rate compared with placebo. We tested the non-inferiority of basiliximab vs rabbit anti-thymocyte globulin (RATG) on the incidence of acute rejection 6 months after transplantation. Methods: From July 2002 to April 2004, 35 patients were enrolled in a multicenter, parallel group, open-label, non-inferiority trial. Patients were randomized to receive induction treatment with basiliximab (20 mg on Day 0 and 4) or RANG (125 mg on Day 0, 1, and 2). Standard maintenance therapy with cyclosporine, mycophenolate mofetil, and prednisone was used. Results: Seventeen patients (aged 54 +/- 9 years old) received basiliximab, and 18 patients (aged 54 +/- 12 years old) received RATG. The freedom rate of rejection at 6 months (grade 3A or more) averaged 65% (11/17) with basiliximab and 83% (15/18) with RATG. The upper limit of the 1-sided 90% confidence interval for the difference RATG-basiliximab was 37.2%, exceeding the 22.5% non-inferiority margin. CD3 and CD4 levels were higher (p < 0.0001 for both), whereas CD25/CD4 and CD25/CD8 levels were lower (p < 0.0001 and p = 0.0462, respectively) in patients treated with basiliximab. One of the 14 basiliximab patients showed detectable cytomegalovirus viral load during the first 3 months after transplantation, whereas cytomegalovirus was detected by quantitative polymerase chain reaction in the plasma of 5 of the 13 RATG patients (p = 0.0505). Conclusion: Non-inferiority of basiliximab treatment for prophylaxis of acute rejection after heart transplantation could not be shown. RANG administration is associated with a higher rate of asymptomatic cytomegalovirus viral load detection in the plasma.