Neonates with symptomatic congenital CMV disease, with or without CNS involvement, were eligible for enrollment. Given the rarity of this disease, 40 study sites participated, and each was anticipated to contribute only a few study participants. All the study participants had CMV detected in urine or throat-swab specimens by means of culture, shell-vial culture, or polymerase-chain-reaction assay. Symptomatic disease was defined as one or more of the following: thrombocytopenia, petechiae, hepatomegaly, splenomegaly, intrauterine growth restriction, hepatitis, or CNS involvement such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid indexes, chorioretinitis, sensorineural hearing loss, or the detection of CMV DNA in cerebrospinal fluid. Eligible participants had a gestational age of 32 weeks or more, were 30 days of age or less, and weighed at least 1800 g at the initiation of therapy.
The institutional review board at each study center approved the study protocol. After written informed consent was obtained from the parent or legal guardian, all participants received valganciclovir (at a dose of 16 mg per kilogram of body weight, orally twice daily) for 6 weeks.15 (link) Participants then underwent randomization in a 1:1 ratio to receive either continued valganciclovir or placebo for 4.5 months. The dose of the study medication was adjusted monthly for growth. Study drugs (oral valganciclovir and placebo) were provided by Hoffmann–La Roche, which had no role in the study design or data analyses or in the writing of the manuscript or the decision to submit it for publication. Study personnel and the participants’ families were unaware of the randomization assignments.
The primary end point prespecified in the protocol was the change in hearing in the better ear (“best-ear” hearing), from baseline to the 6-month follow-up.13 (link) Secondary end points prespecified in the protocol included the change in total-ear hearing (i.e., hearing in one or both ears that could be evaluated) from baseline to follow-up at 6, 12, and 24 months; change in best-ear hearing from baseline to follow-up at 12 and 24 months; neurologic impairment at 12 and 24 months; and adverse events leading to the permanent discontinuation of therapy. Tertiary end points included the correlation of viral load in whole blood with audiologic and neurodevelopmental outcomes, adverse events related to the study medication, and characterization of blood concentrations of ganciclovir.
The institutional review board at each study center approved the study protocol. After written informed consent was obtained from the parent or legal guardian, all participants received valganciclovir (at a dose of 16 mg per kilogram of body weight, orally twice daily) for 6 weeks.15 (link) Participants then underwent randomization in a 1:1 ratio to receive either continued valganciclovir or placebo for 4.5 months. The dose of the study medication was adjusted monthly for growth. Study drugs (oral valganciclovir and placebo) were provided by Hoffmann–La Roche, which had no role in the study design or data analyses or in the writing of the manuscript or the decision to submit it for publication. Study personnel and the participants’ families were unaware of the randomization assignments.
The primary end point prespecified in the protocol was the change in hearing in the better ear (“best-ear” hearing), from baseline to the 6-month follow-up.13 (link) Secondary end points prespecified in the protocol included the change in total-ear hearing (i.e., hearing in one or both ears that could be evaluated) from baseline to follow-up at 6, 12, and 24 months; change in best-ear hearing from baseline to follow-up at 12 and 24 months; neurologic impairment at 12 and 24 months; and adverse events leading to the permanent discontinuation of therapy. Tertiary end points included the correlation of viral load in whole blood with audiologic and neurodevelopmental outcomes, adverse events related to the study medication, and characterization of blood concentrations of ganciclovir.