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Everolimus with reduced cyclosporine versus MMF with standard cyclosporine in de novo heart transplant recipients.

AbstractBACKGROUND:
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.
AuthorsHans 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
JournalTransplantation (Transplantation) Vol. 88 Issue 1 Pg. 115-22 (Jul 15 2009) ISSN: 1534-6080 [Electronic] United States
PMID19584690 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Creatinine
  • Mycophenolic Acid
  • Sirolimus
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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