Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial

Am J Transplant. 2012 Nov;12(11):3021-30. doi: 10.1111/j.1600-6143.2012.04231.x. Epub 2012 Sep 4.

Abstract

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acyclovir / administration & dosage
  • Administration, Oral
  • Antiviral Agents / administration & dosage*
  • Benzimidazoles / administration & dosage*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Ganciclovir / administration & dosage
  • Graft Rejection / prevention & control*
  • Graft Rejection / virology
  • Graft Survival
  • Humans
  • Liver Transplantation / adverse effects
  • Liver Transplantation / immunology
  • Liver Transplantation / methods*
  • Male
  • Postoperative Complications / drug therapy
  • Postoperative Complications / virology
  • Prospective Studies
  • Ribonucleosides / administration & dosage*
  • Risk Assessment
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Ribonucleosides
  • Ganciclovir
  • maribavir
  • Acyclovir