Valganciclovir for symptomatic congenital cytomegalovirus disease

David W Kimberlin; Penelope M Jester; Pablo J Sánchez; Amina Ahmed; Ravit Arav-Boger; Marian G Michaels; Negar Ashouri; Janet A Englund; Benjamin Estrada; Richard F Jacobs; José R Romero; Sunil K Sood; M Suzanne Whitworth; Mark J Abzug; Mary T Caserta; Sandra Fowler; Jorge Lujan-Zilbermann; Gregory A Storch; Roberta L DeBiasi; Jin-Young Han; April Palmer; Leonard B Weiner; Joseph A Bocchini; Penelope H Dennehy; Adam Finn; Paul D Griffiths; Suzanne Luck; Kathleen Gutierrez; Natasha Halasa; James Homans; Andi L Shane; Michael Sharland; Kari Simonsen; John A Vanchiere; Charles R Woods; Diane L Sabo; Inmaculada Aban; Huichien Kuo; Scott H James; Mark N Prichard; Jill Griffin; Dusty Giles; Edward P Acosta; Richard J Whitley; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group

doi:10.1056/NEJMoa1404599

Valganciclovir for symptomatic congenital cytomegalovirus disease

David W Kimberlin, Penelope M Jester, Pablo J Sánchez, Amina Ahmed, Ravit Arav-Boger, Marian G Michaels, Negar Ashouri, Janet A Englund, Benjamin Estrada, Richard F Jacobs, José R Romero, Sunil K Sood, M Suzanne Whitworth, Mark J Abzug, Mary T Caserta, Sandra Fowler, Jorge Lujan-Zilbermann, Gregory A Storch, Roberta L DeBiasi, Jin-Young HanApril Palmer, Leonard B Weiner, Joseph A Bocchini, Penelope H Dennehy, Adam Finn, Paul D Griffiths, Suzanne Luck, Kathleen Gutierrez, Natasha Halasa, James Homans, Andi L Shane, Michael Sharland, Kari Simonsen, John A Vanchiere, Charles R Woods, Diane L Sabo, Inmaculada Aban, Huichien Kuo, Scott H James, Mark N Prichard, Jill Griffin, Dusty Giles, Edward P Acosta, Richard J Whitley, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group

Research output: Contribution to journal › Article (Academic Journal) › peer-review

601 Citations (Scopus)

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). Total-ear 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. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

Original language	English
Pages (from-to)	933-943
Number of pages	11
Journal	New England Journal of Medicine
Volume	372
Issue number	10
DOIs	https://doi.org/10.1056/NEJMoa1404599
Publication status	Published - 5 Mar 2015

Keywords

Antiviral Agents
Audiometry
Child Development
Cytomegalovirus Infections
Double-Blind Method
Drug Administration Schedule
Evoked Potentials, Auditory, Brain Stem
Ganciclovir
Gestational Age
Hearing Loss, Sensorineural
Humans
Infant, Newborn
Neutropenia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1056/NEJMoa1404599

Handle.net

Persistent link

Professor Adam H R Finn
- Adam.Finnbristol.acuk
- Bristol Medical School (PHS) - Professor of Paediatrics
- Bristol Population Health Science Institute
- Health Protection Research Unit (HPRU)
- Infection and Immunity
- Bristol Children's Vaccine Centre
Person: Academic , Member, Group lead

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., ... National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (2015). Valganciclovir for symptomatic congenital cytomegalovirus disease. New England Journal of Medicine, 372(10), 933-943. https://doi.org/10.1056/NEJMoa1404599

@article{91219627819a46239ff575ffe87dbff8,

title = "Valganciclovir for symptomatic congenital cytomegalovirus disease",

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). Total-ear 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. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).",

keywords = "Antiviral Agents, Audiometry, Child Development, Cytomegalovirus Infections, Double-Blind Method, Drug Administration Schedule, Evoked Potentials, Auditory, Brain Stem, Ganciclovir, Gestational Age, Hearing Loss, Sensorineural, Humans, Infant, Newborn, Neutropenia",

author = "Kimberlin, {David W} and Jester, {Penelope M} and S{\'a}nchez, {Pablo J} and Amina Ahmed and Ravit Arav-Boger and Michaels, {Marian G} and Negar Ashouri and Englund, {Janet A} and Benjamin Estrada and Jacobs, {Richard F} and Romero, {Jos{\'e} R} and Sood, {Sunil K} and Whitworth, {M Suzanne} and Abzug, {Mark J} and Caserta, {Mary T} and Sandra Fowler and Jorge Lujan-Zilbermann and Storch, {Gregory A} and DeBiasi, {Roberta L} and Jin-Young Han and April Palmer and Weiner, {Leonard B} and Bocchini, {Joseph A} and Dennehy, {Penelope H} and Adam Finn and Griffiths, {Paul D} and Suzanne Luck and Kathleen Gutierrez and Natasha Halasa and James Homans and Shane, {Andi L} and Michael Sharland and Kari Simonsen and Vanchiere, {John A} and Woods, {Charles R} and Sabo, {Diane L} and Inmaculada Aban and Huichien Kuo and James, {Scott H} and Prichard, {Mark N} and Jill Griffin and Dusty Giles and Acosta, {Edward P} and Whitley, {Richard J} and {National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group}",

year = "2015",

month = mar,

day = "5",

doi = "10.1056/NEJMoa1404599",

language = "English",

volume = "372",

pages = "933--943",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "10",

}

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, J-Y, 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, K, Vanchiere, JA, Woods, CR, Sabo, DL, Aban, I, Kuo, H, James, SH, Prichard, MN, Griffin, J, Giles, D, Acosta, EP, Whitley, RJ & National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group 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

TY - JOUR

T1 - Valganciclovir for symptomatic congenital cytomegalovirus disease

AU - Kimberlin, David W

AU - Jester, Penelope M

AU - Sánchez, Pablo J

AU - Ahmed, Amina

AU - Arav-Boger, Ravit

AU - Michaels, Marian G

AU - Ashouri, Negar

AU - Englund, Janet A

AU - Estrada, Benjamin

AU - Jacobs, Richard F

AU - Romero, José R

AU - Sood, Sunil K

AU - Whitworth, M Suzanne

AU - Abzug, Mark J

AU - Caserta, Mary T

AU - Fowler, Sandra

AU - Lujan-Zilbermann, Jorge

AU - Storch, Gregory A

AU - DeBiasi, Roberta L

AU - Han, Jin-Young

AU - Palmer, April

AU - Weiner, Leonard B

AU - Bocchini, Joseph A

AU - Dennehy, Penelope H

AU - Finn, Adam

AU - Griffiths, Paul D

AU - Luck, Suzanne

AU - Gutierrez, Kathleen

AU - Halasa, Natasha

AU - Homans, James

AU - Shane, Andi L

AU - Sharland, Michael

AU - Simonsen, Kari

AU - Vanchiere, John A

AU - Woods, Charles R

AU - Sabo, Diane L

AU - Aban, Inmaculada

AU - Kuo, Huichien

AU - James, Scott H

AU - Prichard, Mark N

AU - Griffin, Jill

AU - Giles, Dusty

AU - Acosta, Edward P

AU - Whitley, Richard J

AU - National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group

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). Total-ear 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. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

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). Total-ear 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. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

KW - Antiviral Agents

KW - Audiometry

KW - Child Development

KW - Cytomegalovirus Infections

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Evoked Potentials, Auditory, Brain Stem

KW - Ganciclovir

KW - Gestational Age

KW - Hearing Loss, Sensorineural

KW - Humans

KW - Infant, Newborn

KW - Neutropenia

U2 - 10.1056/NEJMoa1404599

DO - 10.1056/NEJMoa1404599

M3 - Article (Academic Journal)

C2 - 25738669

SN - 0028-4793

VL - 372

SP - 933

EP - 943

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 10

ER -

Valganciclovir for symptomatic congenital cytomegalovirus disease

Abstract

Keywords

UN SDGs

Access to Document

Handle.net

Fingerprint

Profiles

Professor Adam H R Finn

Cite this