Summary

for people ages 1 month to 5 months (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

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 maximum worsening in left or right ear hearing 8 months after randomization compared to untreated cCMV-infected hearing impaired infants. Main Secondary Objectives: 1. To determine if valganciclovir treatment improves the following outcomes when compared to the control group: 1. The risk of a clinically significant worsening of hearing defined by occurrence of cochlear implantation due to progressive hearing loss or a ≥ 10 dB (decibel) increase in the minimum response level (MRL) at two or more audiometric test frequencies (from among 1 kHz, 2 kHz, and 4kHz) in either the left or right ear or a ≥ 15 dB increase at any of these frequencies in either the left or right ear between baseline and 8 months post-randomization. 2. The MacArthur-Bates Communicative Development Inventory (CDI) percentile score for words produced at 22 months of age. 3. The change in the average MRL across the 2 and 4 kHz frequencies from baseline to 8 months post-randomization in the best-ear. 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.

Official Title

Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants: ValEAR Trial

Details

Cytomegalovirus (CMV) can be transmitted from the mother to the fetus and is a leading cause of sensorineural hearing loss (SNHL), which is a condition where the inner ear is unable to convert sound into nerve impulses to the brain. This hearing loss and its detrimental effect on language development contribute nearly $4 billion annually to the health care costs in the U.S. Unlike other types of SNHL, CMV induced hearing loss can be treated. Several clinical trials have demonstrated that antiviral therapy may prevent progressive hearing loss if administered early in life for severely affected (symptomatic CMV) infants. These promising findings have given rise to a debate regarding the best method for identifying and treating the more numerous asymptomatic CMV-infected infants.

One approach is to conduct universal newborn hearing screens, and then do CMV diagnostic testing only on the infants who fail the hearing screen. This targeted approach should identify those infants at greatest risk of developing progressive hearing loss and consequent communicative difficulties. Utah is the first state to mandate this approach whereby infants under three weeks of age who fail their newborn hearing screening undergo CMV testing. In this trial, the hearing screen targeted approach will be used to identify patients eligible for participation in a double blind placebo controlled randomized clinical trial of antiviral valganciclovir therapy. The results of this trial will inform public policy, potentially shift our current clinical practice regarding pediatric hearing loss evaluation, and potentially offer a therapeutic option to asymptomatic CMV-infected infants with SNHL.

Keywords

Cmv Congenital CMV Congenital Cmv SNHL Sensorineural Hearing Loss valganciclovir Hearing Loss Hearing Loss, Sensorineural Deafness Ganciclovir Simple Syrup

Eligibility

You can join if…

Open to people ages 1 month to 5 months

  • Age greater than or equal to 1 month and less than or equal to 6 months at the time of randomization; AND
  • Greater than or equal to 37 weeks gestational age at birth; 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.

You CAN'T join if...

  • 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/mm3, Hemoglobin less than 8 g/dL,or platelets less than 50,000/mm3, splenomegaly, or significant hematologic disorders(e.g., hemophilia, leukemia, sickle cell anemia); OR

  • Creatinine clearance less than 60 mL/min/1.73m2 or significant renal disorders (e.g.,nephrotic syndrome); OR

  • Potassium greater than 5.5 mEq/L; 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.

Locations

  • UCSF Benioff Children's Hospital not yet accepting patients
    San Francisco California 94158 United States
  • Lucile Packard Children's Hospital not yet accepting patients
    Palo Alto California 94304 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Albert Park
ID
NCT03107871
Phase
Phase 3
Study Type
Interventional
Last Updated
June 7, 2018