Immunosuppression
A Multicenter, Prospective, Randomized, Double-Blind Trial of Basiliximab in Heart Transplantation

https://doi.org/10.1016/j.healun.2004.09.010Get rights and content

Background

The role and pharmacokinetics of interleukin-2 (IL-2) monoclonal antibodies (mAbs) in heart transplantation remain unclear. This 1-year double-blind, randomized, placebo-controlled study evaluated safety, tolerability, and pharmacokinetics of the IL-2 mAb basiliximab with cyclosporine, mycophenolate mofetil, and steroids in adult de novo heart transplant recipients.

Methods

Fifty-six patients received either basiliximab (20 mg) or placebo on Days 0 and 4 post-transplantation. Safety assessments included adverse events, serious adverse events, and infections. The time to and severity of biopsy-proven acute rejection (BPAR) were also assessed.

Results

Basiliximab was generally well tolerated. There were no significant differences between treatment groups with respect to adverse event profiles, serious adverse events (84.0% vs 61.3%), or infections (84% vs 74.2%). The mean number of days to first BPAR was longer with basiliximab (73.7 ± 59.68) than placebo (40.6 ± 53.30) at 6 months, but not statistically significant (trend). The duration that basiliximab concentrations exceeded the CD25 saturation threshold averaged 38 ± 13 days. Patients with rejection did not clear basiliximab faster or have shorter durations of saturation than rejection-free patients. None of the patients screened had detectable anti-idiotype antibodies.

Conclusions

These pilot results describe the pharmacokinetics of basiliximab and show that basiliximab appears to be tolerated with a similar safety profile to placebo in adult de novo heart transplant recipients. Larger scale clinical trials are feasible and warranted.

Section snippets

Study Design

This was a multicenter, double-blind, randomized pilot study conducted at 5 sites in the United States. Heart transplant recipients were randomized (computer generated) in a 1:1 ratio to receive a first dose of either basiliximab or placebo within 4 to 6 hours after separation from cardiopulmonary bypass (Figure 1). On Day 4 post-transplantation, patients received a second dose of study medication. Patients were then followed for 1 year, in which the first 6 months were double-blind.

Patient Population

Patients

Results

Fifty-six heart transplant recipients were randomized to double-blind treatment at 5 transplant centers. Of these, 25 (44.6%) patients were treated with basiliximab and 31 (55.4%) patients received placebo. Four patients died: 3 (12%) in the basiliximab group and 1 (3.2%) in the placebo group. Of the 3 deaths in the basiliximab group, 1 each was attributed to a cerebral hemorrhage (Day 11), aspiration (Day 33), and a multilobular pneumonia at Day 244. The death in the placebo group was

Discussion

The primary objective of this pilot study was to assess the safety and tolerability of basiliximab in de novo heart transplant recipients and more important, to evaluate its pharmacokinetics. Basiliximab was generally well tolerated and exhibited an overall safety profile comparable with placebo during the first year post-transplantation. The adverse events seen in basiliximab-treated patients were typical of those observed in heart transplantation. These findings are consistent with those of

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    This study was supported by a grant from Novartis Pharmaceuticals Corporation.

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