title: Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients.
abstract: We compared the efficacy and safety of valganciclovir with those of oral ganciclovir in preventing cytomegalovirus (CMV) disease in high-risk seronegative solid organ transplant (SOT) recipients of organs from seropositive donors (D+/R-). In this randomised, prospective, double-blind, double-dummy study, 364 CMV D+/R- patients received valganciclovir 900 mg once daily or oral ganciclovir 1000 mg three times a day (tid) within 10 days of transplant and continued through 100 days. CMV disease, plasma viremia, acute graft rejection, graft loss and safety were analyzed up to 6 and 12 months post-transplant. Endpoint committee-defined CMV disease developed in 12.1% and 15.2% of valganciclovir and ganciclovir patients, respectively, by 6 months, though with a difference in the relative efficacy of valganciclovir and ganciclovir between organs (i.e. an organ type-treatment interaction). By 12 months, respective incidences were 17.2% and 18.4%, and the incidence of investigator-treated CMV disease events was comparable in the valganciclovir (30.5%) and ganciclovir (28.0%) arms. CMV viremia during prophylaxis was significantly lower with valganciclovir (2.9% vs. 10.4%; p=0.001), but was comparable by 12 months (48.5% valganciclovir vs 48.8% ganciclovir). Time-to-onset of CMV disease and to viremia were delayed with valganciclovir; rates of acute allograft rejection were generally lower with valganciclovir. Except for a higher incidence of neutropenia with valganciclovir (8.2%, vs 3.2% ganciclovir) the safety profile was similar for both drugs. Overall, once-daily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients.
authors.affiliation: Mayo Clinic, Rochester, MN, USA. paya@lilly.com
authors.forename: Carlos
authors.initials: C
authors.lastname: Paya
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
authors.forename: Ed
authors.initials: E
authors.lastname: Dominguez
authors.forename: Kenneth
authors.initials: K
authors.lastname: Washburn
authors.forename: Emily
authors.initials: E
authors.lastname: Blumberg
authors.forename: Barbara
authors.initials: B
authors.lastname: Alexander
authors.forename: Richard
authors.initials: R
authors.lastname: Freeman
authors.forename: Nigel
authors.initials: N
authors.lastname: Heaton
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pescovitz
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D019540:Area Under Curve; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications; D011446:Prospective Studies; D013997:Time Factors; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir