Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants (ValEAR)
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|ClinicalTrials.gov Identifier: NCT03107871|
Recruitment Status : Recruiting
First Posted : April 11, 2017
Last Update Posted : July 29, 2019
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:
To determine if valganciclovir treatment improves the following outcomes when compared to the control group:
- 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.
- The MacArthur-Bates Communicative Development Inventory (CDI) percentile score for words produced at 22 months of age.
- The change in the average MRL across the 2 and 4 kHz frequencies from baseline to 8 months post-randomization in the best-ear.
- To evaluate safety measures based on all grade 3 or greater new adverse events designated by the NIAID Division of AIDS (DAIDS) toxicity tables.
|Condition or disease||Intervention/treatment||Phase|
|Cmv Congenital CMV Congenital Cmv SNHL Sensorineural Hearing Loss||Drug: Valganciclovir Drug: Simple Syrup||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||108 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Placebo and active drug will be dispensed in identical amber bottles with identical labeling.|
|Official Title:||Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants: ValEAR Trial|
|Actual Study Start Date :||August 31, 2018|
|Estimated Primary Completion Date :||July 2022|
|Estimated Study Completion Date :||July 2024|
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.
Other Name: Sucrose Water
- Best-Ear Hearing Score [ Time Frame: Assessed at 8 months post-randomization ]The maximum worsening in left or right ear hearing 8 months after randomization compared to untreated cCMV-infected hearing impaired infants will be measured.
- Clinically Significant Worsening of Total-Ear Hearing [ Time Frame: Assessed at 8 months post-randomization ]The risk of a clinically significant worsening of hearing defined by occurrence of cochlear implantation due to progressive hearing loss or a ≥ 10 dB 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.
- Communicative Development Outcome [ Time Frame: Assessed at 14 months of age ]The MacArthur-Bates Communicative Development Inventory (CDI) percentile score for words produced at 22 months of age.
- Change in Best-Ear Hearing [ Time Frame: Assessed at 8 months post-randomization ]The change in the average MRL across the 2 and 4 kHz frequencies from baseline to 8 months post-randomization in the best-ear.
- Additional hearing endpoints [ Time Frame: Between baseline and the 8 and 20 months post-randomization assessments. ]Hearing aid use, cochlear implantation and/or changes in the MRL's at frequencies 1 kHz, 2 kHz, and 4 kHz, between the baseline assessment and the 8 and 20 months post-randomization assessments will be measured.
- Communicative development endpoint One [ Time Frame: Assessed at 14 and 22 months of age ]Subscales of the MacArthur-Bates CDI will be measured.
- Communicative development endpoint Two [ Time Frame: Assessed at 14 and 22 months of age ]Scores from the Ages and Stages Questionnaire 3rd edition (ASQ-3) will be measured.
- Communicative development endpoint Three [ Time Frame: Assessed at 14 and 22 months of age ]The total score from the LittlEARS Auditory Questionnaire will be measured.
- Valganciclovir Pharmacokinetics [ Time Frame: From week 2 to month 6 post-randomization ]Valganciclovir drug levels will be measured.
- Viral Resistance [ Time Frame: Assessed at month 7 post-randomization ]The presence of viral resistance will be measured.
- Viral Load [ Time Frame: Assessed at baseline month 3, and month 7 post-randomization ]Viral load will be measured
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03107871
|Contact: Stephanie Dorton, BSNfirstname.lastname@example.org|
|Contact: Kaitlin C Stephens, MBAemail@example.com|
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|Principal Investigator:||Albert Park, MD||University of Utah|