Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants

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Brief Title

Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants

Official Title

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

Brief 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.
    

Detailed Description

      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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Best-Ear Hearing Score

Secondary Outcome

 Clinically Significant Worsening of Total-Ear Hearing

Condition

Cmv Congenital

Intervention

Valganciclovir

Study Arms / Comparison Groups

 Arm A
Description:  Valganciclovir 16 mg/kg PO twice daily (BID) x 6 months

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

108

Start Date

August 31, 2018

Completion Date

July 2024

Primary Completion Date

July 2022

Eligibility Criteria

        Inclusion Criteria:

          -  Age greater than or equal to 1 month and less than or equal to 6 months at the time of
             randomization; 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.

        Exclusion Criteria:

          -  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/mm^3, Hemoglobin less than 8 g/dL,
             or platelets less than 50,000/mm^3, splenomegaly, or significant hematologic disorders
             (e.g., hemophilia, leukemia, sickle cell anemia); OR

          -  Creatinine clearance less than 60 mL/min/1.73m^2 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; OR

          -  < 32 weeks gestational age at birth; OR

          -  Weight at the time of birth < 1800 g.
      

Gender

All

Ages

1 Month - 5 Months

Accepts Healthy Volunteers

No

Contacts

Albert Park, MD, 801-587-7758, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03107871

Organization ID

90760

Secondary IDs

1U01DC014706-01A1

Responsible Party

Sponsor-Investigator

Study Sponsor

Albert Park

Collaborators

 National Institute on Deafness and Other Communication Disorders (NIDCD)

Study Sponsor

Albert Park, MD, Principal Investigator, University of Utah


Verification Date

April 2019