Abstract | BACKGROUND: Pharmacokinetic modeling supports trough monitoring of everolimus, but prospective data comparing this approach versus mycophenolate mofetil (MMF) in de novo cardiac transplant recipients are currently unavailable. METHODS: In a 12-month multicenter open-label study, cardiac transplant patients received everolimus (trough level 3-8 ng/mL) with reduced cyclosporine A (CsA) or MMF (3 g/day) with standard CsA, both with corticosteroids+/-induction therapy. RESULTS: In total, 176 patients were randomized ( everolimus 92, MMF 84). Mean creatinine clearance was 72.5+/-27.9 and 76.8+/-32.1 mL/min at baseline, 65.4+/-24.7 and 72.2+/-26.2 mL/min at month 6, and 68.7+/-27.7 and 71.8+/-29.8 mL/min at month 12 with everolimus and MMF, respectively. The primary endpoint was not met since calculated CrCl at month 6 posttransplant was 6.9 mL/min lower with everolimus, exceeding the predefined margin of 6 mL/min. However, by month 12 the between-group difference had narrowed versus baseline (3.1 mL/min). All efficacy endpoints were noninferior for everolimus versus MMF. The 12-month incidence of biopsy-proven acute rejection International Heart and Lung Transplantation grade more than or equal to 3A was 21 of 92 (22.8%) with everolimus and 25 of 84 (29.8%) with MMF. Adverse events were consistent with class effects including less-frequent cytomegalovirus infection with everolimus (4 [4.4%]) than MMF (14 [16.9%], P=0.01). CONCLUSION: Concentration-controlled everolimus with reduced CsA results in similar renal function and equivalent efficacy compared with MMF with standard CsA at 12 months after cardiac transplantation.
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Authors | Hans B Lehmkuhl, José Arizon, Mario Viganò, Luis Almenar, Gino Gerosa, Massimo Maccherini, Shaida Varnous, Francesco Musumeci, J Mark Hexham, Kevin C Mange, Ugolino Livi, 2411 Study Investigators |
Journal | Transplantation
(Transplantation)
Vol. 88
Issue 1
Pg. 115-22
(Jul 15 2009)
ISSN: 1534-6080 [Electronic] United States |
PMID | 19584690
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenal Cortex Hormones
- Immunosuppressive Agents
- Cyclosporine
- Everolimus
- Creatinine
- Mycophenolic Acid
- Sirolimus
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Topics |
- Adrenal Cortex Hormones
(administration & dosage)
- Adult
- Biopsy
- Creatinine
(blood)
- Cyclosporine
(administration & dosage, adverse effects)
- Drug Therapy, Combination
- Europe
- Everolimus
- Female
- Graft Rejection
(etiology, pathology, prevention & control)
- Heart Transplantation
(adverse effects)
- Humans
- Immunosuppressive Agents
(administration & dosage, adverse effects)
- Kidney
(drug effects, physiopathology)
- Kidney Diseases
(chemically induced, physiopathology, prevention & control)
- Kidney Function Tests
- Male
- Middle Aged
- Mycophenolic Acid
(administration & dosage, adverse effects, analogs & derivatives)
- Sirolimus
(administration & dosage, adverse effects, analogs & derivatives)
- Time Factors
- Treatment Outcome
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