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. Han & 24 others A. 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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