Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients.
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.
Paya
Carlos
C
Mayo Clinic, Rochester, MN, USA. paya@lilly.com
Humar
Atul
A
Dominguez
Ed
E
Washburn
Kenneth
K
Blumberg
Emily
E
Alexander
Barbara
B
Freeman
Richard
R
Heaton
Nigel
N
Pescovitz
Mark D
MD
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
D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir