Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants

The overall goal of this study is to determine the clinical benefit and safety of antiviral therapy for asymptomatic congenital cytomegalovirus (cCMV) infected hearing-impaired infants. We will conduct a multi-center double-blind randomized placebo-controlled trial to determine whether hearing-impaired infants with asymptomatic cCMV have better hearing and language outcomes if they receive valganciclovir antiviral treatment. We will also determine the safety of antiviral valganciclovir therapy for asymptomatic cCMV-infected hearing impaired infants. This study will be unique in that the cohort enrolled will only include hearing-impaired infants with asymptomatic cCMV. Primary Objective: To determine if treatment of cCMV-infected hearing impaired infants with isolated hearing loss with the antiviral drug valganciclovir reduces the mean slope of total hearing thresholds over the 20 months after randomization compared to untreated cCMV-infected infants with isolated hearing loss. Main Secondary Objectives: 1. To determine if valganciclovir treatment improves the following outcomes when compared to the control group: 1. The slope of best ear hearing thresholds over the 20 months after randomization. 2. The MacArthur-Bates Communicative Development Inventory (CDI) percentile score for words produced at 20 months of age. 2. To evaluate safety measures based on all grade 3 or greater new adverse events designated by the NIAID Division of AIDS (DAIDS) toxicity tables.

Inclusion Criteria: * Age greater than or equal to 1 month and less than or equal to 12 months at the time of randomization; AND * Positive congenital CMV by urine culture or polymerase chain reaction test(PCR), OR saliva culture or PCR followed by confirmatory urine PCR by 21 days of age, OR urine culture or PCR after 21 days of age followed by newborn dry blood spot PCR; AND * Confirmed sensorineural hearing loss (SNHL) by auditory brainstem response (ABR) testing. For ABR assessments, hearing loss is defined as levels greater than 25 dB normal hearing levels (NHL) at 1, 2, or 4 kHz in one or both ears. Exclusion Criteria: * Imminent demise; OR * Known hypersensitivity reaction to valganciclovir, ganciclovir, or any components of the investigational product formulation; OR * ALT (Alanine Aminotransferase) five times baseline U/L, hepatomegaly, or significant gastrointestinal disorders (e.g., eosinophilic esophagitis, ulcerative colitis); OR * Absolute neutrophil count (ANC) less than 500 cells/mm\^3, Hemoglobin less than 8 g/dL, or platelets less than 50,000/mm\^3, splenomegaly, or significant hematologic disorders (e.g., hemophilia, leukemia, sickle cell anemia); OR * Creatinine clearance less than 60 mL/min/1.73m\^2 or significant renal disorders (e.g., nephrotic syndrome); OR * Receiving other antiviral medications or immune globulin therapy; OR * Receiving other investigational drugs; OR * Breast feeding from a mother receiving antiviral or immunosuppressive medication; OR * Known HIV positive mother (risk of immunosuppression); OR * Subject is currently using list of prohibited medication specified by the package insert; OR * Other known cause contributing to SNHL (e.g., meningitis, aminoglycoside ototoxicity); OR * Bilateral profound SNHL or auditory neuropathy spectrum disorder; OR * Existing conductive hearing loss or mixed permanent hearing loss is present; OR * Evidence of intracranial calcification; OR * Evidence of hydrocephalus; OR * Microcephaly; OR * Presence of petechiae; OR * Intrauterine growth retardation; OR * Chorioretinitis, optic atrophy or pale optic nerves; OR * Parent or guardian unable to speak English or Spanish; OR * Subject exposed to a language other than English or Spanish a majority of the time; OR * Subject unable to complete hearing assessments or parent/guardian unable to complete communication questionnaires; OR * \< 32 weeks gestational age at birth; OR * Weight at the time of birth \< 1800 g.