Evaluation of Long-term Efficacy of 4 to 6-month Course Antiviral Therapy for Neurodevelopmental Impairments Caused by Congenital Cytomegalovirus Infection: A Multicenter, Randomized, Controlled, Non-inferiority Clinical Trial

Title: Evaluation of Long-term Efficacy of 4-month versus 6-month Course Antiviral Therapy for Neurodevelopmental Impairment Caused by Congenital CMV Infection: A Multicenter, Randomized, Controlled, Non-inferiority Clinical Study

1. Background and Rationale：Congenital cytomegalovirus (cCMV) infection is a leading cause of childhood neurodevelopmental disability and sensorineural hearing loss (SNHL). International guidelines, based on evidence from high-income countries, recommend a 6-month antiviral course for symptomatic infection. However, clinical practice in China lags significantly, still adhering to a 3-4 week regimen due to a lack of high-quality domestic evidence. Preliminary data suggest a 4-month course may be non-inferior to the 6-month standard by potentially aligning with the transition from productive to latent infection around 4 months of age. This study aims to address this critical evidence gap.2. Study Objectives：Primary: To evaluate the impact of intermediate (4-month) versus long (6-month) course antiviral therapy on long-term neurodevelopmental outcomes in infants with moderate-to-severe cCMV infection, and to establish a novel diagnostic and therapeutic framework.Secondary: To identify high-risk factors associated with adverse long-term outcomes.3. Study Design and Methods：This is a prospective, multicenter, randomized, open-label, parallel-controlled, non-inferiority clinical trial.Participants: Newborns (≤30 days old) diagnosed with moderate-to-severe cCMV infection. Key exclusion criteria include gestational age <32 weeks, birth weight <1.8 kg, and coexisting genetic/metabolic diseases.Randomization & Intervention: Eligible subjects will be block-randomized 1:1 via a computer-generated sequence.Experimental Group: Receives 4 months of antiviral therapy.Control Group: Receives 6 months of antiviral therapy (current international standard).Both groups receive either intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily).Sample Size: A total of 150 subjects will be enrolled (60 from the lead center), anticipating 126 evaluable cases at study completion (2 years of age) to demonstrate non-inferiority with a margin (Δ) of 20%, 80% power, and a one-sided alpha of 0.025.4. Evaluation and Endpoints：Primary Outcome: Composite poor neurodevelopmental outcome at 12 months of age, defined as (1) death, or (2) moderate/severe impairment, including cerebral palsy, epilepsy, moderate-to-severe SNHL (>40 dB threshold and/or requiring cochlear implantation), visual impairment, or a score <-2 SD on standardized developmental scales (Griffiths, BSID-II, or Bayley-III).Secondary Outcomes: Include mild neurodevelopmental impairment at 12 months, and poor/mild neurodevelopmental outcomes at 24 months.Assessments: Scheduled follow-ups include clinical, laboratory (hepatic/renal function, CMV DNA load), and instrumental evaluations (neuroimaging, audiology, ophthalmology) during treatment and at 6, 12, and 24 months of age.5. Data Management and Ethics：Data will be managed using a multicenter Electronic Data Capture (EDC) system with double data entry. The study protocol has been approved by the Medical Ethics Committee of Children's Hospital, Zhejiang University School of Medicine. Written informed consent will be obtained from all participants' guardians. The study is scheduled from January 2026 to December 2028.This study will provide crucial high-level evidence to inform optimal antiviral therapy duration for cCMV infection in China, with the goal of improving long-term child health outcomes and reducing disease burden.