Clinical Trial: Short-Term vs. Long-Term Valganciclovir Therapy for Symptomatic Congenital CMV Infections

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase III, Randomized, Placebo-Controlled Blinded Investigation of Six Weeks vs. Six Months of Oral Valganciclovir Therapy in Infants With Symptomatic Congenital Cytomegaloviru

Brief Summary: Cytomegalovirus (CMV) infection is known to cause hearing loss and mental retardation. The purpose of this study is to compare a 6-week course to a 6-month course of the drug valganciclovir in babies born with CMV to assess the safety and efficacy of this treatment. Participants will include 104 infants (30 days old or younger) born with CMV disease. All infants will take valganciclovir by mouth for 6 weeks. At the end of the 6 week period, subjects will be assigned by chance to receive either valganciclovir or placebo (inactive substance) to complete the 6 months of antiviral treatment. Patients will be followed for the study related evaluations of safety, changes to hearing, and developmental milestones for up to 2 years. Patients will be followed by telephone contact for an additional 3 years. Thus, participants may be involved in study related procedures for approximately 5 years.

Detailed Summary: This study is a multi-center, prospective, international, Phase III, randomized and blinded investigation of 6 weeks versus 6 months of oral valganciclovir therapy in babies with symptomatic congenital cytomegalovirus (CMV) disease. Following enrollment, study subjects will receive 6 weeks of oral valganciclovir. Near the end of the 6-week course, subjects will be randomized in a 1:1 fashion either to continue on valganciclovir to complete 6 months of therapy or to begin a matching placebo to complete the 6 months. Study subjects will be stratified according to whether or not there is central nervous system (CNS) involvement at study entry. During the 6-month treatment period and the 1 month thereafter, study subjects will be followed weekly for 4 weeks, then every other week for 8 weeks, then every month for 4 months. At each of these visits, safety labs will be checked, growth parameters recorded, and adverse events assessed. The dose of study medication will be adjusted for weight gain at each of these study visits. Dose adjustments may also occur as indicated per protocol for neutropenia, thrombocytopenia, or renal impairment. Whole blood will be obtained for CMV viral load at each of these visits as well. Hearing outcomes will be assessed at baseline, 6 months, 12 months and 24 months. Developmental outcomes will be assessed at 12 months and 24 months. Changes in whole blood viral load measurements will be correlated with both hearing and neurologic outcomes. In study subjects with increasing whole blood viral loads during the course of treatment, assessment for antiviral resistance may be undertaken.Safety assessments include: hematology labs, chemistry labs, physical examinations, and adverse event data performed/collected serially. Development of neutropenia will be confirmed by repeat blood testing within one week, and study drug will be held until it resolves. Efficacy assessments include: hearing assessments at baseline, 6 months, 12 months and 24 months;
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome: Change in Best Ear Hearing Assessments at 6 Months. [ Time Frame: Between baseline and 6 months ]

Hearing assessment was evaluated by an independent audiologist. At baseline, a brainstem evoked response (BSER) assessment and autoacoustic emissions (OAEs) hearing assessments were obtained. At 6 months, BSER and /or Visual reinforcement audiometry (VRA) and OAEs were obtained. A single, independent study audiologist who was blinded to treatment assignment assessed the audiology test battery for each subject and assigned the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications were assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. Following this, the study audiologist assigned the "best ear" classification for the subject at that study visit; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification was mild hearing loss.


Original Primary Outcome:

Current Secondary Outcome:

  • Adverse Events Which Lead to Permanent Discontinuation of Valganciclovir Therapy or Lead to Irreversible Outcome of the Adverse Event. [ Time Frame: baseline through 7 months ]
    Adverse events were assessed at each visit through month 7 of the study. No subject discontinued valganciclovir therapy due to permanent discontinuation of valganciclovir therapy or lead to irreversible outcome of any adverse event.
  • Change in Best Ear Hearing Assessments at 12 Months. [ Time Frame: Between baseline and 12 months ]
    Hearing assessment was evaluated by an independent audiologist. At baseline, a brainstem evoked response (BSER) assessment and autoacoustic emissions (OAEs) hearing assessments were obtained. At 12 months, BSER and /or Visual reinforcement audiometry (VRA) and OAEs were obtained. A single, independent study audiologist who was blinded to treatment assignment assessed the audiology test battery for each subject and assigned the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications were assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. Following this, the study audiologist assigned the "best ear" classification for the subject at that study visit; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification was mild hearing loss.
  • Change in Best Ear Hearing Assessments at 24 Months. [ Time Frame: Between baseline and 24 months ]
    Hearing assessment was evaluated by an independent audiologist. At baseline, a brainstem evoked response (BSER) assessment and autoacoustic emissions (OAEs) hearing assessments were obtained. At 24 months, BSER and /or Visual reinforcement audiometry (VRA) and OAEs were obtained. A single, independent study audiologist who was blinded to treatment assignment assessed the audiology test battery for each subject and assigned the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications were assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. Following this, the study audiologist assigned the "best ear" classification for the subject at that study visit; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification was mild hearing loss.
  • Number of Ears With Improvement or Protected Hearing in Hearing Assessments Over Left and Right Ears at 6 Months.(Based on 84 Ears From 43 Placebo Subjects and 82 Ears From 43 Valganciclovir Subjects) [ Time Frame: Between baseline and 6 months ]
    Hearing assessment was evaluated by an independent audiologist. At baseline, a brainstem evoked response (BSER) assessment and autoacoustic emissions (OAEs) hearing assessments were obtained. At 6 months, BSER and /or Visual reinforcement audiometry (VRA) and OAEs were obtained. A single, independent study audiologist who was blinded to treatment assignment assessed the audiology test battery for each subject and assigned the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications were assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. Following this, the study audiologist assigned the "best ear" classification for the subject at that study visit; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification was mild hearing loss.
  • Number of Ears With Improvement or Protected Hearing in Hearing Assessments Over Left and Right Ears at 12 Months.(Based on 77 Ears From 40 Placebo Subjects and 79 Ears From 41 Valganciclovir Subjects) [ Time Frame: Between baseline and 12 months ]
    Hearing assessment was evaluated by an independent audiologist. At baseline, a brainstem evoked response (BSER) assessment and autoacoustic emissions (OAEs) hearing assessments were obtained. At 12 months, BSER and /or Visual reinforcement audiometry (VRA) and OAEs were obtained. A single, independent study audiologist who was blinded to treatment assignment assessed the audiology test battery for each subject and assigned the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications were assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. Following this, the study audiologist assigned the "best ear" classification for the subject at that study visit; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification was mild hearing loss.
  • Number of Ears With Improvement or Protected Hearing Assessments Over Left and Right Ears at 24 Months.(Based on 58 Ears From 31 Placebo Subjects and 70 Ears From 37 Valganciclovir Subjects) [ Time Frame:&nb

    Original Secondary Outcome:

    Information By: National Institute of Allergy and Infectious Diseases (NIAID)

    Dates:
    Date Received: April 26, 2007
    Date Started: June 2008
    Date Completion:
    Last Updated: August 13, 2015
    Last Verified: July 2015