Utility of oral valganciclovir for the treatment of cytomegalovirus disease after renal transplantation


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Abstract

SYNOPSISBACKGROUNDStandard therapy for cytomegalovirus (CMV) disease in recipients of solid organ transplants comprises intravenous ganciclovir, which is costly and inconvenient to administer.OBJECTIVETo compare the efficacy and safety of intravenous ganciclovir with that of its orally administered prodrug, valganciclovir, for the treatment of CMV disease after solid organ transplantation.DESIGNThis open-label, noninferiority trial ('VICTOR') enrolled adult solid organ transplant recipients from five continents who had CMV in their blood and symptoms consistent with CMV disease. Life-threatening CMV disease, resistance to ganciclovir, and Cockcroft-Gault-estimated creatinine clearance <10 ml/min were among the exclusion criteria.INTERVENTIONParticipants were randomized to receive induction treatment with either oral valganciclovir 900 mg twice daily or intravenous ganciclovir 5 mg/kg twice daily, for 21 days. After 21 days, patients in both groups underwent maintenance treatment with valganciclovir 900 mg/day for 28 days. Doses of both drugs were adjusted according to Cockcroft-Gault-estimated creatinine clearance. Use of other antiviral agents (such as aciclovir), interferons and CMV hyperimmune globulin was prohibited. CMV load was measured with a polymerase chain reaction assay at baseline, on days 3, 7, 10, 14, 17 and 21, and weekly thereafter until study end (49 days).OUTCOME MEASURESThe primary end point was eradication of CMV viremia, defined as <600 virus copies per ml plasma, after 21 days. Secondary end points included the rate of clinical resolution of CMV disease and the rate of adverse events.RESULTSA total of 333 patients were screened between April 2004 and June 2006. Of the 321 patients who comprised the intention-to-treat population, 164 (122 kidney transplant recipients) had been randomized to receive valganciclovir and 157 (115 kidney transplant recipients) to receive ganciclovir. Clinical presentation of CMV disease, incidence of previous anti-CMV therapy, and baseline CMV serostatus were similar in the two groups. By day 21, CMV viremia had been eradicated in 45.1% (74) of the valganciclovir-treated patients and in 48.4% (76) of the ganciclovir-treated patients (95% CI for difference −14% to 8%); therefore, valganciclovir met the noninferiority criterion of achieving 50% eradication, within a range of −15%. Rates of viral eradication remained comparable for valganciclovir and ganciclovir at study end (67.1% [110 patients] and 70.1% [110 patients], respectively). Rates of clinical resolution were similar in the two groups at 21 days (77.4% [127 patients] for valganciclovir; 80.3% [126 patients] for ganciclovir) and at 49 days (85.4% [140 patients] and 84.1% [132 patients], respectively). The kinetics of viral eradication were also similar in the two groups, according to the per-protocol analysis. There were no differences in the rates of treatment discontinuation or adverse events between the groups.CONCLUSIONOral valganciclovir is not inferior to intravenous ganciclovir for the treatment of CMV disease in renal transplant recipients and has a similar adverse event profile.

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