Daclizumab to Prevent Rejection after Cardiac Transplantation - Daclizumab to Prevent Rejection after Cardiac Transplantation
The goal of the trial was to evaluate treatment with daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, compared with placebo among patients undergoing first cardiac transplantation.
Patients Enrolled: 434
Mean Follow Up: 12 months
Mean Patient Age: Mean age 53 years
Age >13 years; first cardiac transplantation.
Known need for cytolytic therapy at the time of transplantation; need for ventricular assist devices after surgery.
Composite of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up at 6 months
Patients at 31 sites undergoing first cardiac transplantation were randomized to daclizumab (n=216) or placebo (n=218). All patients were also treated with cyclosporine, mycophenolate mofetil, corticosteroids, and statin. Daclizumab (1 mg/kg intravenous, up to 100 mg) was started within 12 hours after transplantation and on days 8, 22, 36 and 50.
Indication for transplantation was dilated cardiomyopathy in 64% of patients and coronary artery disease in 30% of patients. UNOS wait-list status was 1A in 22% of patients, 1B in 39% of patients, and 2 in 38% of patients. Left ventricular assist devices were present in 8% of patients. At least 4 doses of study drug were given in 81.8% of patients.
The primary composite endpoint of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up at 6 months was significantly lower in the daclizumab group compared with placebo (35.6% vs 47.7%, p=0.007), driven primarily by biopsy proven rejection (25.5% vs 41.3%). At 12 months, the primary endpoint trended lower in the daclizumab group compared with placebo (44.9% vs 53.2%, p=0.06). Mortality at 12 months was 9.7% in the daclizumab group vs 5.5% in the placebo group (p=0.11). Among the subgroup of patients who received cytolytic therapy for 12 months (n=77), death from infection was higher in the daclizumab group (15% vs 0%). Frequency of opportunistic infection was similar in both groups (32.9% for daclizumab vs 38.6% for placebo), as were cancer rates (5.1% vs 5.3%, respectively).
Among patients undergoing first cardiac transplantation and treated with triple immunosuppresive therapy, additional treatment with the monoclonal antibody daclizumab was associated with a reduction in the primary composite endpoint at 6 months, driven primarily by biopsy proven rejection, compared with placebo. This reduction in rejection did not correlate with an increase in opportunistic infections. Despite the reduction in the primary endpoint, mortality trended higher in the daclizumab group. The authors suggested the increased mortality may be explained in part by the increase in fatal infections when daclizumab was administered along with cytolytic therapy.
Hershberger RE. Daclizumab to Prevent Rejection after Cardiac Transplantation. N Engl J Med 2005;352:2705-13.
Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Heart Failure, Novel Agents, Heart Transplant, Mechanical Circulatory Support, Interventions and Coronary Artery Disease
Keywords: Antibodies, Monoclonal, Humanized, Cyclosporine, Immunoglobulin G, Coronary Artery Disease, Neoplasms, Follow-Up Studies, Heart-Assist Devices, Biopsy, Immunosuppressive Agents, Heart Transplantation, Receptors, Interleukin-2, Cardiomyopathy, Dilated, Opportunistic Infections
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