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

Primary Purpose

Cytomegalovirus Infection

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Placebo

Valganciclovir

About this trial

This is an interventional treatment trial for Cytomegalovirus Infection focused on measuring Cytomegalovirus, congenital, infants

Eligibility Criteria

undefined - 30 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed informed consent from parent(s) or legal guardian(s)
Confirmation of cytomegalovirus (CMV) from urine or throat swab specimens by culture, shell vial, or polymerase chain reaction (PCR) tests
Symptomatic congenital CMV disease, as manifest by one or more of the following:
1. Thrombocytopenia
2. Petechiae
3. Hepatomegaly
4. Splenomegaly
5. Intrauterine growth restriction
6. Hepatitis (elevated transaminases and/or bilirubin)
7. Central nervous system (CNS) involvement of the CMV disease [such as microcephaly, radiographic abnormalities indicative of CMV CNS disease, abnormal cerebrospinal fluid (CSF) indices for age, chorioretinitis, hearing deficits as detected by formal brainstem evoked response (not a screening auditory brainstem response {ABR}), and/or positive CMV PCR from CSF]
Less than or equal to 30 days of age at study enrollment
Weight at study enrollment greater than or equal to 1800 grams
Gestational age greater than or equal to 32 weeks at birth

Exclusion Criteria:

Imminent demise
Patients receiving other antiviral agents or immune globulin
Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis)
Documented renal insufficiency, as noted by a creatinine clearance less than 10 mL/min/1.73m^2 at time of study enrollment
Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, or maribivir
Infants known to be born to women who are human immunodeficiency virus (HIV) positive (but HIV testing is not required for study entry)
Current receipt of other investigational drugs

Sites / Locations

University of Alabama - Children's of Alabama - Clinical Virology
University of South Alabama - Children's Specialty Clinic
Arkansas Children's Hospital - Infectious Diseases
Los Angeles County - University of Southern California - Medical Center - Pediatrics
Plaza Towers Obstetrics and Gynecology
Children's Hospital of Orange County - Infectious Diseases
Stanford University School of Medicine
Children's Hospital Colorado - Infectious Disease
Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease
University of Florida - College of Medicine - Jacksonville
University of South Florida - Tampa General Hospital - Pediatrics
Emory Children's Center - Pediatric Infectious Diseases
University of Louisville School of Medicine - Kosair Childrens Hospital - Infectious Diseases
Tulane University - Tulane Medical Center - Pediatrics
Louisiana State University Health Shreveport - Pediatrics
Johns Hopkins Children's Center - Pediatric Infectious Diseases
Children's Hospital Boston - Infectious Diseases
University of Minnesota - Pediatric Infectious Disease
University of Mississippi - Children's Infectious Diseases
Children's Mercy Hospital and Clinics - Infectious Diseases
Washington University School of Medicine in St. Louis - Center for Clinical Studies
Creighton University Medical Center - Medicine - Infectious Diseases
Childrens Hospital at Saint Peters University Hospital - Allergy, Immunology and Infectious Diseases
Robert Wood Johnson Medical School - Pediatrics
Women & Children's Hospital of Buffalo - Infectious Diseases
Cohen Children's Medical Center - Pediatric Infectious Diseases
University of Rochester Medical Center - Golisano Children's Hospital - Infectious Diseases
SUNY Upstate Medical University Hospital - Pediatrics
Carolinas Medical Center - Pediatrics - Infectious Diseases
MetroHealth Medical Center - Pediatric Infectious Disease
Cleveland Clinic Main Campus - Center for Pediatric Infectious Diseases
Nationwide Children's Hospital - Infectious Diseases
Children's Hospital of Pittsburgh of UPMC - Pediatric Infectious Diseases
Rhode Island Hospital - Pediatrics
Medical University of South Carolina - Pediatrics - Infectious Diseases
Vanderbilt University - Pediatric - Infectious Diseases
Children's Medical Center Dallas - Neonatal ICU
University of Texas Southwestern Medical Center - Pediatrics
Cook Children's Infectious Disease Services
University of Utah - Pediatric Pharmacology Program
Seattle Children's Hospital - Infectious Diseases
Bristol Royal Hospital for Children - UBHT Education Centre
University College London - Royal Free Campus - Virology
Saint George's Hospital - Pediatric Infectious Diseases
John Radcliffe Hospital
Birmingham Heartlands Hospital
Alder Hey Childrens Hospital
Newcastle General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Valganciclovir

Placebo

Arm Description

Six months of oral Valganciclovir.

Six weeks of oral Valganciclovir followed by placebo to complete the six month time period.

Outcomes

Primary Outcome Measures

Change in Best Ear Hearing Assessments at 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.

Secondary Outcome Measures

Adverse Events Which Lead to Permanent Discontinuation of Valganciclovir Therapy or Lead to Irreversible Outcome of the Adverse Event.

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.

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.

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)

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)

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)

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 Hearing Deterioration Over Left and Right Ears at 6 Months.(Based on 84 Ears From 43 Placebo Subjects and 82 Ears From 43 Valganciclovir Subjects)

Number of Ears With Hearing Deterioration Over Left and Right Ears at 12 Months.(Based on 77 Ears From 40 Placebo Subjects and 79 Ears From 41 Valganciclovir Subjects)

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 Hearing Deterioration Over Left and Right Ears at 24 Months.(Based on 58 Ears From 31 Placebo Subjects and 70 Ears From 37 Valganciclovir Subjects)

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.

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Cognitive Composite Score).

Cognitive Composite Score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Composite Scores, the range of scores is between 40 (very poor cognitive skills) and 160 (excellent cognitive skills), with the average cogonitive skills score for a child (age adjusted) is 100 with standard deviation of 15.

Neurological Impairment at 12 Months of Age Utilizing the Bayley Scales of Infant and Toddler Development (Receptive Communication Scaled Score).

Receptive Communication Scaled Score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Scaled Scores, the range of scores is between 1 (very poor receptive communication skills) and 19 (excellent receptive communication skills), with the average receptive communication skills score for a child (age adjusted) is 10 with standard deviation of 3.

Neurological Impairment at 12 Months of Age Utilizing the Bayley Scales of Infant and Toddler Development (Expressive Communication Scaled Score).

Expressive Communication Scaled Score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Scaled Scores, the range of scores is between 1 (very poor expressive communication skills) and 19 (excellent expressive communication skills), with the average expressive communication skills score for a child (age adjusted) is 10 with standard deviation of 3.

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Language Composite Score).

Language Composite Score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Composite Scores, the range of scores is between 40 (very poor language skills) and 160 (excellent language skills), with the average language skills score for a child (age adjusted) is 100 with standard deviation of 15.

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Fine Motor Scaled Score).

Fine Motor Scaled Score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Scaled Scores, the range of scores is between 1 (very poor fine motor skills) and 19 (excellent fine motor skills), with the average fine motor skills score for a child (age adjusted) is 10 with standard deviation of 3.

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Gross Motor Scaled Score).

Gross Motor Scaled Score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Scaled Scores, the range of scores is between 1 (very poor gross motor skills) and 19 (excellent gross motor skills), with the average gross motor skills score for a child (age adjusted) is 10 with standard deviation of 3.

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Motor Composite Score).

Motor Composite Score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Composite Scores, the range of scores is between 40 (very poor motor skills) and 160 (excellent motor skills), with the average motor skills score for a child (age adjusted) is 100 with standard deviation of 15.

Neurological Impairment at 24 Months Utilizing the Bayley Scales of Infant and Toddler Development (Receptive Communication Scaled Score).

Receptive Communication Scaled score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Scaled Scores, the range of scores is between 1 (very poor receptive communication skills) and 19 (excellent receptive communication skills), with the average receptive communication skills score for a child (age adjusted) is 10 with standard deviation of 3.

Neurological Impairment at 24 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Cognitive Composite Score).

Cognitive Composite Score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Composite Scores, the range of scores are between 40 (very poor cognitive skills) and 160 (excellent cognitive skills), with the average cognitive skills score for a child (age adjusted) is 100 with standard deviation of 15.

Neurological Impairment at 24 Months of Life, Utilizing the Bayley Scales of Infant and Toddler Development (Expressive Communication Scaled Score).

Neurologic Impairment at 24 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Language Composite Score).

Neurological Impairment at 24 Months, Utilizing the Bayley Scales of Infant and Toddler Development (Fine Motor Scaled Score).

Fine motor scaled score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Scaled Scores, the range of scores is between 1 (very poor fine motor skills) and 19 (excellent fine motor skills), with the average fine motor skills score for a child (age adjusted) is 10 with standard deviation of 3.

Neurological Impairment at 24 Months of Life, Utilizing the Bayley Scales of Infant and Toddler Development (Gross Motor Scaled Score).

Gross motor scaled score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring is between 1 (very poor gross motor skills) and 19 (excellent gross motor skills), with the average gross motor skills score for a child (age adjusted) is 10 with standard deviation of 3.

Neurological Impairment at 24 Months of Life, Utilizing the Bayley Scales of Infant and Toddler Development (Motor Composite Score).

Motor composite score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Composite Scores, the range of scores is between 40 (very poor motor skills) and 160 (excellent motor skills), with the average motor skills score for a child (age adjusted) is 100 with standard deviation of 15.

Full Information

NCT ID

NCT00466817

First Posted

April 26, 2007

Last Updated

August 13, 2015

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT00466817

Brief Title

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

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 Cytomegalovirus Infection (CASG 112)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2015

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

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 Description

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; and neurodevelopmental assessments at 12 months and 24 months. Study objectives are: to compare the impact on hearing outcomes of 6 weeks versus 6 months of antiviral treatment with valganciclovir oral solution in infants with symptomatic congenital CMV disease; to compare the safety profile of 6 weeks versus 6 months of antiviral therapy with valganciclovir oral solution in infants with symptomatic congenital CMV disease; to compare the impact on neurologic outcomes of 6 weeks versus 6 months of antiviral treatment with valganciclovir oral solution in infants with symptomatic congenital CMV disease; and to correlate change in whole blood viral load with hearing and neurologic outcomes. Participants will include 104 male and female neonates (less than or equal to 30 days) with symptomatic congenital CMV.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cytomegalovirus Infection

Keywords

Cytomegalovirus, congenital, infants

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

109 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Valganciclovir

Arm Type

Experimental

Arm Description

Six months of oral Valganciclovir.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Six weeks of oral Valganciclovir followed by placebo to complete the six month time period.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

9 grams of powder which contains no Valganciclovir free base. The oral solution formulation comprises the following excipients: mannitol, lactose anhydrous, fumaric acid, sodium benzoate, saccharin sodium, flavor, and purified water.

Intervention Type

Drug

Intervention Name(s)

Valganciclovir

Intervention Description

Mono-valyl ester pro-drug of ganciclovir, oral solution, provided as a 12 grams of powder containing 5 grams of Valganciclovir free base. The oral solution formulation comprises the following excipients: Providone K30, fumaric acid, sodium benzoate, sodium saccharin, mannitol, flavor, and purified water.

Primary Outcome Measure Information:

Title

Change in Best Ear Hearing Assessments at 6 Months.

Description

Time Frame

Between baseline and 6 months

Secondary Outcome Measure Information:

Title

Adverse Events Which Lead to Permanent Discontinuation of Valganciclovir Therapy or Lead to Irreversible Outcome of the Adverse Event.

Description

Time Frame

baseline through 7 months

Title

Change in Best Ear Hearing Assessments at 12 Months.

Description

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.

Time Frame

Between baseline and 12 months

Title

Change in Best Ear Hearing Assessments at 24 Months.

Description

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.

Time Frame

Between baseline and 24 months

Title

Description

Time Frame

Between baseline and 6 months

Title

Description

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.

Time Frame

Between baseline and 12 months

Title

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)

Description

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.

Time Frame

Between baseline and 24 months

Title

Number of Ears With Hearing Deterioration Over Left and Right Ears at 6 Months.(Based on 84 Ears From 43 Placebo Subjects and 82 Ears From 43 Valganciclovir Subjects)

Description

Time Frame

Between baseline and 6 months

Title

Number of Ears With Hearing Deterioration Over Left and Right Ears at 12 Months.(Based on 77 Ears From 40 Placebo Subjects and 79 Ears From 41 Valganciclovir Subjects)

Description

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.

Time Frame

Between baseline and 12 months

Title

Number of Ears With Hearing Deterioration Over Left and Right Ears at 24 Months.(Based on 58 Ears From 31 Placebo Subjects and 70 Ears From 37 Valganciclovir Subjects)

Description

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.

Time Frame

Between baseline and 24 months

Title

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Cognitive Composite Score).

Description

Time Frame

12 Months after enrollment

Title

Neurological Impairment at 12 Months of Age Utilizing the Bayley Scales of Infant and Toddler Development (Receptive Communication Scaled Score).

Description

Time Frame

12 Months after enrollment

Title

Neurological Impairment at 12 Months of Age Utilizing the Bayley Scales of Infant and Toddler Development (Expressive Communication Scaled Score).

Description

Time Frame

12 Months after enrollment

Title

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Language Composite Score).

Description

Time Frame

12 Months after enrollment

Title

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Fine Motor Scaled Score).

Description

Time Frame

12 Months after enrollment

Title

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Gross Motor Scaled Score).

Description

Time Frame

12 Months after enrollment

Title

Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Motor Composite Score).

Description

Time Frame

12 Months after enrollment

Title

Neurological Impairment at 24 Months Utilizing the Bayley Scales of Infant and Toddler Development (Receptive Communication Scaled Score).

Description

Time Frame

24 Months after enrollment

Title

Neurological Impairment at 24 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Cognitive Composite Score).

Description

Cognitive Composite Score for infants and toddlers was measured by use of the Bayley Scales of Infant and Toddler Development. For the Bayleys scoring of the Composite Scores, the range of scores are between 40 (very poor cognitive skills) and 160 (excellent cognitive skills), with the average cognitive skills score for a child (age adjusted) is 100 with standard deviation of 15.

Time Frame

24 months after enrollment

Title

Neurological Impairment at 24 Months of Life, Utilizing the Bayley Scales of Infant and Toddler Development (Expressive Communication Scaled Score).

Description

Time Frame

24 Months after enrollment

Title

Neurologic Impairment at 24 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Language Composite Score).

Description

Time Frame

24 Months after enrollment

Title

Neurological Impairment at 24 Months, Utilizing the Bayley Scales of Infant and Toddler Development (Fine Motor Scaled Score).

Description

Time Frame

24 Months after enrollment

Title

Neurological Impairment at 24 Months of Life, Utilizing the Bayley Scales of Infant and Toddler Development (Gross Motor Scaled Score).

Description

Time Frame

24 Months after enrollment.

Title

Neurological Impairment at 24 Months of Life, Utilizing the Bayley Scales of Infant and Toddler Development (Motor Composite Score).

Description

Time Frame

24 Months after enrollment

10. Eligibility

Sex

All

Maximum Age & Unit of Time

30 Days

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Signed informed consent from parent(s) or legal guardian(s) Confirmation of cytomegalovirus (CMV) from urine or throat swab specimens by culture, shell vial, or polymerase chain reaction (PCR) tests Symptomatic congenital CMV disease, as manifest by one or more of the following: Thrombocytopenia Petechiae Hepatomegaly Splenomegaly Intrauterine growth restriction Hepatitis (elevated transaminases and/or bilirubin) Central nervous system (CNS) involvement of the CMV disease [such as microcephaly, radiographic abnormalities indicative of CMV CNS disease, abnormal cerebrospinal fluid (CSF) indices for age, chorioretinitis, hearing deficits as detected by formal brainstem evoked response (not a screening auditory brainstem response {ABR}), and/or positive CMV PCR from CSF] Less than or equal to 30 days of age at study enrollment Weight at study enrollment greater than or equal to 1800 grams Gestational age greater than or equal to 32 weeks at birth Exclusion Criteria: Imminent demise Patients receiving other antiviral agents or immune globulin Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis) Documented renal insufficiency, as noted by a creatinine clearance less than 10 mL/min/1.73m^2 at time of study enrollment Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, or maribivir Infants known to be born to women who are human immunodeficiency virus (HIV) positive (but HIV testing is not required for study entry) Current receipt of other investigational drugs

Facility Information:

Facility Name

University of Alabama - Children's of Alabama - Clinical Virology

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35233-1711

Country

United States

Facility Name

University of South Alabama - Children's Specialty Clinic

City

Mobile

State/Province

Alabama

ZIP/Postal Code

36604-3207

Country

United States

Facility Name

Arkansas Children's Hospital - Infectious Diseases

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72202-3500

Country

United States

Facility Name

Los Angeles County - University of Southern California - Medical Center - Pediatrics

City

Los Angeles

State/Province

California

ZIP/Postal Code

90033-1075

Country

United States

Facility Name

Plaza Towers Obstetrics and Gynecology

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048-5970

Country

United States

Facility Name

Children's Hospital of Orange County - Infectious Diseases

City

Orange

State/Province

California

ZIP/Postal Code

92868-3835

Country

United States

Facility Name

Stanford University School of Medicine

City

Stanford

State/Province

California

ZIP/Postal Code

94305-2200

Country

United States

Facility Name

Children's Hospital Colorado - Infectious Disease

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045-7106

Country

United States

Facility Name

Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20010-2916

Country

United States

Facility Name

University of Florida - College of Medicine - Jacksonville

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209-6511

Country

United States

Facility Name

University of South Florida - Tampa General Hospital - Pediatrics

City

Tampa

State/Province

Florida

ZIP/Postal Code

33606-3438

Country

United States

Facility Name

Emory Children's Center - Pediatric Infectious Diseases

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322-1014

Country

United States

Facility Name

University of Louisville School of Medicine - Kosair Childrens Hospital - Infectious Diseases

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202-1821

Country

United States

Facility Name

Tulane University - Tulane Medical Center - Pediatrics

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70112-2600

Country

United States

Facility Name

Louisiana State University Health Shreveport - Pediatrics

City

Shreveport

State/Province

Louisiana

ZIP/Postal Code

71103-4228

Country

United States

Facility Name

Johns Hopkins Children's Center - Pediatric Infectious Diseases

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287-0011

Country

United States

Facility Name

Children's Hospital Boston - Infectious Diseases

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115-5711

Country

United States

Facility Name

University of Minnesota - Pediatric Infectious Disease

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455-0341

Country

United States

Facility Name

University of Mississippi - Children's Infectious Diseases

City

Jackson

State/Province

Mississippi

ZIP/Postal Code

39216-4505

Country

United States

Facility Name

Children's Mercy Hospital and Clinics - Infectious Diseases

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64108-4619

Country

United States

Facility Name

Washington University School of Medicine in St. Louis - Center for Clinical Studies

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110-1010

Country

United States

Facility Name

Creighton University Medical Center - Medicine - Infectious Diseases

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68131-2137

Country

United States

Facility Name

Childrens Hospital at Saint Peters University Hospital - Allergy, Immunology and Infectious Diseases

City

New Brunswick

State/Province

New Jersey

ZIP/Postal Code

08901-1766

Country

United States

Facility Name

Robert Wood Johnson Medical School - Pediatrics

City

New Brunswick

State/Province

New Jersey

ZIP/Postal Code

08901-1935

Country

United States

Facility Name

Women & Children's Hospital of Buffalo - Infectious Diseases

City

Buffalo

State/Province

New York

ZIP/Postal Code

14222-2006

Country

United States

Facility Name

Cohen Children's Medical Center - Pediatric Infectious Diseases

City

Manhasset

State/Province

New York

ZIP/Postal Code

11030-3816

Country

United States

Facility Name

University of Rochester Medical Center - Golisano Children's Hospital - Infectious Diseases

City

Rochester

State/Province

New York

ZIP/Postal Code

14642-0001

Country

United States

Facility Name

SUNY Upstate Medical University Hospital - Pediatrics

City

Syracuse

State/Province

New York

ZIP/Postal Code

13210-2342

Country

United States

Facility Name

Carolinas Medical Center - Pediatrics - Infectious Diseases

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28203-5812

Country

United States

Facility Name

MetroHealth Medical Center - Pediatric Infectious Disease

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44109-1998

Country

United States

Facility Name

Cleveland Clinic Main Campus - Center for Pediatric Infectious Diseases

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195-0001

Country

United States

Facility Name

Nationwide Children's Hospital - Infectious Diseases

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43205-2664

Country

United States

Facility Name

Children's Hospital of Pittsburgh of UPMC - Pediatric Infectious Diseases

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224-1529

Country

United States

Facility Name

Rhode Island Hospital - Pediatrics

City

Providence

State/Province

Rhode Island

ZIP/Postal Code

02903-4923

Country

United States

Facility Name

Medical University of South Carolina - Pediatrics - Infectious Diseases

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425-8903

Country

United States

Facility Name

Vanderbilt University - Pediatric - Infectious Diseases

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-0011

Country

United States

Facility Name

Children's Medical Center Dallas - Neonatal ICU

City

Dallas

State/Province

Texas

ZIP/Postal Code

75235-7701

Country

United States

Facility Name

University of Texas Southwestern Medical Center - Pediatrics

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390-9063

Country

United States

Facility Name

Cook Children's Infectious Disease Services

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76104-2710

Country

United States

Facility Name

University of Utah - Pediatric Pharmacology Program

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84108-1457

Country

United States

Facility Name

Seattle Children's Hospital - Infectious Diseases

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105-3901

Country

United States

Facility Name

Bristol Royal Hospital for Children - UBHT Education Centre

City

Bristol

State/Province

Bristol, City of

ZIP/Postal Code

BS2 8AE

Country

United Kingdom

Facility Name

University College London - Royal Free Campus - Virology

City

London

State/Province

London, City of

ZIP/Postal Code

NW3 2PF

Country

United Kingdom

Facility Name

Saint George's Hospital - Pediatric Infectious Diseases

City

London

State/Province

London, City of

ZIP/Postal Code

SW17 0QT

Country

United Kingdom

Facility Name

John Radcliffe Hospital

City

Oxford

State/Province

Oxfordshire

ZIP/Postal Code

OX3 9DU

Country

United Kingdom

Facility Name

Birmingham Heartlands Hospital

City

Birmingham

ZIP/Postal Code

B9 5SS

Country

United Kingdom

Facility Name

Alder Hey Childrens Hospital

City

Liverpool

ZIP/Postal Code

L12 2AP

Country

United Kingdom

Facility Name

Newcastle General Hospital

City

Newcastle Upon Tyne

ZIP/Postal Code

NE4 6BE

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

25738669

Citation

Kimberlin DW, Jester PM, Sanchez PJ, Ahmed A, Arav-Boger R, Michaels MG, Ashouri N, Englund JA, Estrada B, Jacobs RF, Romero JR, Sood SK, Whitworth MS, Abzug MJ, Caserta MT, Fowler S, Lujan-Zilbermann J, Storch GA, DeBiasi RL, Han JY, Palmer A, Weiner LB, Bocchini JA, Dennehy PH, Finn A, Griffiths PD, Luck S, Gutierrez K, Halasa N, Homans J, Shane AL, Sharland M, Simonsen K, Vanchiere JA, Woods CR, Sabo DL, Aban I, Kuo H, James SH, Prichard MN, Griffin J, Giles D, Acosta EP, Whitley RJ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015 Mar 5;372(10):933-43. doi: 10.1056/NEJMoa1404599.

Results Reference

derived

Learn more about this trial

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

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