Valganciclovir for symptomatic congenital cytomegalovirus disease.
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.).
The authors' affiliations are listed in the Appendix.
David W
DW
Kimberlin
Penelope M
PM
Jester
Pablo J
PJ
Sánchez
Amina
A
Ahmed
Ravit
R
Arav-Boger
Marian G
MG
Michaels
Negar
N
Ashouri
Janet A
JA
Englund
Benjamin
B
Estrada
Richard F
RF
Jacobs
José R
JR
Romero
Sunil K
SK
Sood
M Suzanne
MS
Whitworth
Mark J
MJ
Abzug
Mary T
MT
Caserta
Sandra
S
Fowler
Jorge
J
Lujan-Zilbermann
Gregory A
GA
Storch
Roberta L
RL
DeBiasi
Jin-Young
JY
Han
April
A
Palmer
Leonard B
LB
Weiner
Joseph A
JA
Bocchini
Penelope H
PH
Dennehy
Adam
A
Finn
Paul D
PD
Griffiths
Suzanne
S
Luck
Kathleen
K
Gutierrez
Natasha
N
Halasa
James
J
Homans
Andi L
AL
Shane
Michael
M
Sharland
Kari
K
Simonsen
John A
JA
Vanchiere
Charles R
CR
Woods
Diane L
DL
Sabo
Inmaculada
I
Aban
Huichien
H
Kuo
Scott H
SH
James
Mark N
MN
Prichard
Jill
J
Griffin
Dusty
D
Giles
Edward P
EP
Acosta
Richard J
RJ
Whitley
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001299:Audiometry; D002657:Child Development; D003586:Cytomegalovirus Infections / Q000150:complications / Q000151:congenital* / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016057:Evoked Potentials, Auditory, Brain Stem; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005865:Gestational Age; D006319:Hearing Loss, Sensorineural / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007231:Infant, Newborn; D009503:Neutropenia / Q000139:chemically induced; D000077562:Valganciclovir
D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir