Valganciclovir for symptomatic congenital cytomegalovirus disease

D. W. Kimberlin, P. M. Jester, P. J. Sánchez, A. Ahmed, R. Arav-Boger, M. G. Michaels, N. Ashouri, J. A. Englund, B. Estrada, R. F. Jacobs, J. R. Romero, S. K. Sood, M. S. Whitworth, M. J. Abzug, M. T. Caserta, S. Fowler, J. Lujan-Zilbermann, G. A. Storch, R. L. DeBiasi, J. Y. HanA. Palmer, L. B. Weiner, J. A. Bocchini, P. H. Dennehy, A. Finn, P. D. Griffiths, S. Luck, K. Gutierrez, N. Halasa, J. Homans, A. L. Shane, M. Sharland, K. Simonsen, J. A. Vanchiere, C. R. Woods, D. L. Sabo, I. Aban, H. Kuo, S. H. James, M. N. Prichard, J. Griffin, D. Giles, E. P. Acosta, R. J. Whitley

Research output: Contribution to journalArticle

266 Scopus citations

Abstract

BACKGROUND The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P = 0.41). Totalear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P = 0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P = 0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P = 0.004) and on the receptive-communication scale (P = 0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P = 0.64). CONCLUSIONS Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term.

Original languageEnglish (US)
Pages (from-to)933-943
Number of pages11
JournalNew England Journal of Medicine
Volume372
Issue number10
DOIs
StatePublished - Mar 5 2015

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Valganciclovir for symptomatic congenital cytomegalovirus disease'. Together they form a unique fingerprint.

  • Cite this

    Kimberlin, D. W., Jester, P. M., Sánchez, P. J., Ahmed, A., Arav-Boger, R., Michaels, M. G., Ashouri, N., Englund, J. A., Estrada, B., Jacobs, R. F., Romero, J. R., Sood, S. K., Whitworth, M. S., Abzug, M. J., Caserta, M. T., Fowler, S., Lujan-Zilbermann, J., Storch, G. A., DeBiasi, R. L., ... Whitley, R. J. (2015). Valganciclovir for symptomatic congenital cytomegalovirus disease. New England Journal of Medicine, 372(10), 933-943. https://doi.org/10.1056/NEJMoa1404599