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, Kari A 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

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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

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Cytomegalovirus
Hearing
Ear
Neutropenia
valganciclovir
Ganciclovir
Therapeutics
Random Allocation
Child Development
Language
Central Nervous System
Randomized Controlled Trials
Communication
Placebos

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kimberlin, D. W., Jester, P. M., Sánchez, P. J., Ahmed, A., Arav-Boger, R., Michaels, M. G., ... 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

Valganciclovir for symptomatic congenital cytomegalovirus disease. / 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.; Han, J. Y.; Palmer, A.; Weiner, L. B.; Bocchini, J. A.; Dennehy, P. H.; Finn, A.; Griffiths, P. D.; Luck, S.; Gutierrez, K.; Halasa, N.; Homans, J.; Shane, A. L.; Sharland, M.; Simonsen, Kari A; Vanchiere, J. A.; Woods, C. R.; Sabo, D. L.; Aban, I.; Kuo, H.; James, S. H.; Prichard, M. N.; Griffin, J.; Giles, D.; Acosta, E. P.; Whitley, R. J.

In: New England Journal of Medicine, Vol. 372, No. 10, 05.03.2015, p. 933-943.

Research output: Contribution to journalArticle

Kimberlin, DW, Jester, PM, Sánchez, PJ, Ahmed, A, Arav-Boger, R, Michaels, MG, Ashouri, N, Englund, JA, Estrada, B, Jacobs, RF, Romero, JR, Sood, SK, Whitworth, MS, Abzug, MJ, Caserta, MT, Fowler, S, Lujan-Zilbermann, J, Storch, GA, DeBiasi, RL, Han, JY, Palmer, A, Weiner, LB, Bocchini, JA, Dennehy, PH, Finn, A, Griffiths, PD, Luck, S, Gutierrez, K, Halasa, N, Homans, J, Shane, AL, Sharland, M, Simonsen, KA, Vanchiere, JA, Woods, CR, Sabo, DL, Aban, I, Kuo, H, James, SH, Prichard, MN, Griffin, J, Giles, D, Acosta, EP & Whitley, RJ 2015, 'Valganciclovir for symptomatic congenital cytomegalovirus disease', New England Journal of Medicine, vol. 372, no. 10, pp. 933-943. https://doi.org/10.1056/NEJMoa1404599
Kimberlin DW, Jester PM, Sánchez PJ, Ahmed A, Arav-Boger R, Michaels MG et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. New England Journal of Medicine. 2015 Mar 5;372(10):933-943. https://doi.org/10.1056/NEJMoa1404599
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. ; Han, J. Y. ; Palmer, A. ; Weiner, L. B. ; Bocchini, J. A. ; Dennehy, P. H. ; Finn, A. ; Griffiths, P. D. ; Luck, S. ; Gutierrez, K. ; Halasa, N. ; Homans, J. ; Shane, A. L. ; Sharland, M. ; Simonsen, Kari A ; Vanchiere, J. A. ; Woods, C. R. ; Sabo, D. L. ; Aban, I. ; Kuo, H. ; James, S. H. ; Prichard, M. N. ; Griffin, J. ; Giles, D. ; Acosta, E. P. ; Whitley, R. J. / Valganciclovir for symptomatic congenital cytomegalovirus disease. In: New England Journal of Medicine. 2015 ; Vol. 372, No. 10. pp. 933-943.
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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.",
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TY - JOUR

T1 - Valganciclovir for symptomatic congenital cytomegalovirus disease

AU - Kimberlin, D. W.

AU - Jester, P. M.

AU - Sánchez, P. J.

AU - Ahmed, A.

AU - Arav-Boger, R.

AU - Michaels, M. G.

AU - Ashouri, N.

AU - Englund, J. A.

AU - Estrada, B.

AU - Jacobs, R. F.

AU - Romero, J. R.

AU - Sood, S. K.

AU - Whitworth, M. S.

AU - Abzug, M. J.

AU - Caserta, M. T.

AU - Fowler, S.

AU - Lujan-Zilbermann, J.

AU - Storch, G. A.

AU - DeBiasi, R. L.

AU - Han, J. Y.

AU - Palmer, A.

AU - Weiner, L. B.

AU - Bocchini, J. A.

AU - Dennehy, P. H.

AU - Finn, A.

AU - Griffiths, P. D.

AU - Luck, S.

AU - Gutierrez, K.

AU - Halasa, N.

AU - Homans, J.

AU - Shane, A. L.

AU - Sharland, M.

AU - Simonsen, Kari A

AU - Vanchiere, J. A.

AU - Woods, C. R.

AU - Sabo, D. L.

AU - Aban, I.

AU - Kuo, H.

AU - James, S. H.

AU - Prichard, M. N.

AU - Griffin, J.

AU - Giles, D.

AU - Acosta, E. P.

AU - Whitley, R. J.

PY - 2015/3/5

Y1 - 2015/3/5

N2 - 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.

AB - 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.

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