Randomized Controlled Trial of Valganciclovir for Asymptomatic Cytomegalovirus Infected Hearing Impaired Infants (ValEAR)
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.
Aim 1: Test the hypothesis that asymptomatic CMV-infected hearing impaired infants treated with antiviral valganciclovir will have better hearing and language outcomes compared with untreated CMV-infected hearing impaired infants.
Aim 2: Evaluate the safety of antiviral valganciclovir therapy for asymptomatic CMV-infected hearing impaired infants.
Aim 3: Evaluate the pharmacokinetics (pK) of valganciclovir using pharmacometrics modeling to develop a population pK model.
|Cmv Congenital CMV Congenital Cmv SNHL Sensorineural Hearing Loss||Drug: Valganciclovir Drug: Simple Syrup||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Placebo and active drug will be dispensed in identical amber bottles with identical labeling.Primary Purpose: Treatment
|Official Title:||Randomized Controlled Trial of Valganciclovir for Asymptomatic Cytomegalovirus Infected Hearing Impaired Infants: ValEAR Trial|
- Best-Ear Hearing Score [ Time Frame: Assessed at 12 months of age ]The primary outcome is defined as the change from baseline to age 12 months in the best-ear hearing score in the hearing score corresponding to the best ear at each time point.
- Substantial Best-Ear Worsening Hearing Composite Outcome [ Time Frame: Assessed at 12 and 24 months of age ]A clinically significant worsening hearing in the best ear will be defined as the occurrence of a) Cochlear implantation or b) a 20 decibel (dB) or greater increase in the best ear minimum response level (MRL) for at least one of the frequencies 1 kilohertz (kHz), 2 kHz, or 4 kHz but no decrease in the best ear MRL at any of these three frequencies.
- Communicative Development Outcome [ Time Frame: Assessed at 12 and 24 months of age ]Communicative development outcome is the MacArthur-Bates Communicative Development Inventory (CDI) summary score. The summary score is defined by averaging the percentile scores of the four domains of this instrument.
|Anticipated Study Start Date:||October 2017|
|Estimated Study Completion Date:||October 2022|
|Estimated Primary Completion Date:||October 2021 (Final data collection date for primary outcome measure)|
Experimental: Arm A
Valganciclovir 16 mg/kg PO twice daily (BID) x 6 months
Valganciclovir is supplied as a powder for reconstitution into an oral solution. The reconstituted solution formulation comprises the following excipients: Povidone K30, fumaric acid, sodium benzoate, saccharin sodium, mannitol, flavor, and purified water.
Other Name: Valcyte
Placebo Comparator: Arm B
Flavored Simple Syrup, volume equivalent to active arm dose, PO BID x 6 months
Drug: Simple Syrup
Simple Syrup contains sucrose 85% weight by volume, purified water, and methyl paraben as a preservative along with natural preservatives. It will be flavored to match the flavor of valganciclovir.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT03107871
|Contact: Stephanie Bisping, BSNemail@example.com|
|Contact: Kaitlin Cooleyfirstname.lastname@example.org|
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|Principal Investigator:||Albert Park, MD||University of Utah|