Basiliximab and rabbit anti-thymocyte 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 RATG (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).


CONCLUSIONS
Non-inferiority of basiliximab treatment for prophylaxis of acute rejection after heart transplantation could not be shown. RATG administration is associated with a higher rate of asymptomatic cytomegalovirus viral load detection in the plasma.
Carrier
Michel
M
Montréal Heart Institute and the Université de Montréal, Montréal, Québec, Canada. michel.carrier@icm-mhi.org
Leblanc
Marie-Hélène
MH
Perrault
Louis P
LP
White
Michel
M
Doyle
Daniel
D
Beaudoin
Danielle
D
Guertin
Marie-Claude
MC
D000208:Acute Disease; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D000077552:Basiliximab; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000821:virology; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab