Evaluation of Long-term Efficacy of 4 to 6-month Course Antiviral Therapy for Neurodevelopmental Impairments Caused by Congenital Cytomegalovirus Infection

NCT07450365 | Not Yet Recruiting Phase 4

• 1 other identifier: 2025-IRB-0548-Y-01
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Congenital CMV Infection

Keywords

Congenital CMV; SNHL; neurodevelopmental outcome

Outcome Measures

Primary Outcomes (7)

• Death

  Occurrence of death from any cause.

  at 12 Months

• Cerebral Palsy (GMFCS level ≥ II)

  Presence of cerebral palsy classified as Gross Motor Function Classification System (GMFCS) level II or higher.

  at 12 months of age

• Behavioral Disorders Requiring Intervention

  Diagnosis of a behavioral disorder (e.g., autism spectrum disorder, attention-deficit/hyperactivity disorder) that necessitates professional intervention (e.g., behavioral therapy, medication).

  at 12 months of age

• Epilepsy

  Diagnosis of epilepsy (recurrent unprovoked seizures) confirmed by a pediatric neurologist.

  at 12 months of age

• Moderate-to-Severe Sensorineural Hearing Loss (SNHL)

  Defined as a hearing threshold \>40 dB in the better ear on auditory brainstem response (ABR) testing and/or meeting clinical criteria for cochlear implantation.

  at 12 months of age

• Visual Impairment

  Presence of extensive retinal exudates, documented visual deficit, or poor visual fixation due to neurological abnormality, as assessed by ophthalmologic examination.

  at 12 months of age

• Significant Developmental Delay

  Score less than -2 standard deviations (SD) below the mean on any of the following standardized developmental scales: Griffiths Mental Development Scales, Bayley Scales of Infant Development-II (BSID-II) Mental Developmental Index (MDI) or Psychomotor Developmental Index (PDI), or Bayley-III Cognitive, Motor, or General IQ composite scores.

  at 12 months of age

Secondary Outcomes (11)

• Mild Neurodevelopmental Impairment

  at 12 months of age

• Composite Poor Neurodevelopmental Outcome

  at 24 months of age

• Mild Neurodevelopmental Impairment at 24 Months

  at 24 months of age

• Incidence of Adverse Events (AEs)

  from start of treatment through 24 months of age

• Incidence of Serious Adverse Events (SAEs)

  from start of treatment through 24 months of age

Study Arms (2)

Intervention group

EXPERIMENTAL

Intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily) was administered for a treatment course of 4 months.

Drug: Intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily) was administered for a treatment course of 4 months.

Control group

OTHER

Patients received a 6-month course of anti-CMV therapy. The treatment regimen consisted of either intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily).

Drug: Patients received a 6-month course of anti-CMV therapy. The treatment regimen consisted of either intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily).

Interventions

Intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily) was administered for a treatment course of 4 months. DRUG

in Intervention group,Intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily) was administered for a treatment course of 4 months.

Also known as: Patients received a 6-month course of anti-CMV therapy. The treatment regimen consisted of either intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily).

Intervention group

Patients received a 6-month course of anti-CMV therapy. The treatment regimen consisted of either intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily). DRUG

Patients received a 6-month course of anti-CMV therapy. The treatment regimen consisted of either intravenous ganciclovir (6 mg/kg, twice daily) or oral valganciclovir (16 mg/kg, twice daily).

Control group

Eligibility Criteria

• Age: 1 Day - 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Confirmed congenital CMV infection (CMV DNA detected in urine, blood, or serum within 21 days after birth).
• Clinical disease classified as moderate or severe symptomatic cCMV infection (defined by involvement of multiple systems, including at least one neurologic finding, or two or more central nervous system findings such as microcephaly, imaging abnormalities, SNHL, chorioretinitis, or positive CMV DNA in CSF).
• Age at enrollment ≤ 30 days.
• Written informed consent obtained from the parent(s) or legal guardian(s).

You may not qualify if:

• Gestational age \< 32 weeks.
• Birth weight \< 1.8 kg.
• Absence of informed consent.
• Confirmed genetic mutations associated with hearing loss (e.g., GJB2).
• Coexisting major genetic or metabolic diseases known to affect neurodevelopment.
• Occurrence of other intracranial infections during the neonatal period.
• Any condition that, in the opinion of the investigator, would make the infant unsuitable for the study or preclude evaluation.

Sponsors & Collaborators

• Hu Bofei: lead
• Zhejiang University School of Medicine, Obstetrics and Gynecology Hospital: collaborator
• Second Affiliated Hospital of Wenzhou Medical University: collaborator
• Jiangxi Maternal and Child Health Hospital: collaborator
• Jiaxing Maternity and Child Health Care Hospital: collaborator
• Ningbo Women & Children's Hospital: collaborator
• Quzhou Maternal and Child Health Care Hospital: collaborator
• Huzhou Maternity and Child Care Hospital: collaborator

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: clinician

Study Record Dates

• First Submitted: February 13, 2026
• First Posted: March 4, 2026
• Study Start: February 15, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share