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 investigatortreated 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, oncedaily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients.

Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients

“…There is an urgent need for an effective oral treatment for pre-emptive CMV therapy, which would enable prevention and treatment of CMV in an outpatient setting leading to reduced patient burden and health-care cost. The finding of the therapeutic equivalence of oral valganciclovir and intravenous ganciclovir is a confirmation of previous reports with respect to pre-emptive [12][13][14]22 and prophylactic treatment 20 in solid organ transplant recipients.…”

“…Ganciclovir and valganciclovir dosages were adjusted to renal function as described previously. 20 During (val)ganciclovir treatment, CMV DNA load and haematological parameters were monitored at least weekly; G-CSF prophylaxis was not routinely used. Donor lymphocyte infusion was not used as a therapeutic modality for CMV infection.…”

Enfermedad por citomegalovirus en pacientes receptores de trasplante de corazón en un centro de referencia nacional

“…La presentación de la enfermedad por CMV ocurre con una mayor frecuencia después de los 100 días 9 ; sin embargo, un tercio de los pacientes post trasplante de órganos sólidos manifiestan la infección antes del año 25 . Todos nuestros pacientes recibieron la quimioprofilaxis; no obstante, dos de ellos desarrollaron la enfermedad después de los 100 días.…”

An assessment of interactions between hepatitis C virus and herpesvirus reactivation in liver transplant recipients using molecular surveillance

“…The parent study was a randomized, multicenter trial assessing the efficacy and safety of valganciclovir (Valcyte; F Hoffmann-La Roche, Basel, Switzerland) and oral ganciclovir (Cymevene/Cytovene; F Hoffman-La Roche) in preventing CMV disease in solid organ transplant recipients. 16 Inclusion and exclusion criteria have been described previously. 16 Briefly, in the parent study, eligible patients were Ն13 yr of age receiving a first liver, heart, kidney, or pancreas allograft with a CMV serostatus of Dϩ/RϪ.…”

“…16 Inclusion and exclusion criteria have been described previously. 16 Briefly, in the parent study, eligible patients were Ն13 yr of age receiving a first liver, heart, kidney, or pancreas allograft with a CMV serostatus of Dϩ/RϪ. The study was approved by the Independent Ethics Committees/Institutional Review Boards of participating centers and was conducted in accordance with the declaration of Helsinki.…”