Cytomegalovirus InfectionPhase 3NCT00466817
Short-Term vs. Long-Term Valganciclovir Therapy for Symptomatic Congenital CMV Infections
A Phase 3 study testing Valganciclovir in people with Cytomegalovirus Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 48 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 30 days
- Conditions the study is for
- Cytomegalovirus Infection
- What is being tested?
- Valganciclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 109 participants
- Where
- 48 sitesin 2 countries
- Study dates
- Jun 2008to Jun 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
48 sites in 2 countries.
48 sites in 2 countries
United States41 sites
Emory Children's Center - Pediatric Infectious Diseases
Atlanta, Georgia, 30322-1014
Children's Hospital Colorado - Infectious Disease
Aurora, Colorado, 80045-7106
Johns Hopkins Children's Center - Pediatric Infectious Diseases
Baltimore, Maryland, 21287-0011
University of Alabama - Children's of Alabama - Clinical Virology
Birmingham, Alabama, 35233-1711
Children's Hospital Boston - Infectious Diseases
Boston, Massachusetts, 02115-5711
Women & Children's Hospital of Buffalo - Infectious Diseases
Buffalo, New York, 14222-2006
Medical University of South Carolina - Pediatrics - Infectious Diseases
Charleston, South Carolina, 29425-8903
Carolinas Medical Center - Pediatrics - Infectious Diseases
Charlotte, North Carolina, 28203-5812
MetroHealth Medical Center - Pediatric Infectious Disease
Cleveland, Ohio, 44109-1998
Cleveland Clinic Main Campus - Center for Pediatric Infectious Diseases
Cleveland, Ohio, 44195-0001
Nationwide Children's Hospital - Infectious Diseases
Columbus, Ohio, 43205-2664
Children's Medical Center Dallas - Neonatal ICU
Dallas, Texas, 75235-7701
University of Texas Southwestern Medical Center - Pediatrics
Dallas, Texas, 75390-9063
Cook Children's Infectious Disease Services
Fort Worth, Texas, 76104-2710
University of Mississippi - Children's Infectious Diseases
Jackson, Mississippi, 39216-4505
University of Florida - College of Medicine - Jacksonville
Jacksonville, Florida, 32209-6511
Children's Mercy Hospital and Clinics - Infectious Diseases
Kansas City, Missouri, 64108-4619
Arkansas Children's Hospital - Infectious Diseases
Little Rock, Arkansas, 72202-3500
Los Angeles County - University of Southern California - Medical Center - Pediatrics
Los Angeles, California, 90033-1075
Plaza Towers Obstetrics and Gynecology
Los Angeles, California, 90048-5970
University of Louisville School of Medicine - Kosair Childrens Hospital - Infectious Diseases
Louisville, Kentucky, 40202-1821
Cohen Children's Medical Center - Pediatric Infectious Diseases
Manhasset, New York, 11030-3816
University of Minnesota - Pediatric Infectious Disease
Minneapolis, Minnesota, 55455-0341
University of South Alabama - Children's Specialty Clinic
Mobile, Alabama, 36604-3207
Vanderbilt University - Pediatric - Infectious Diseases
Nashville, Tennessee, 37232-0011
Childrens Hospital at Saint Peters University Hospital - Allergy, Immunology and Infectious Diseases
New Brunswick, New Jersey, 08901-1766
Robert Wood Johnson Medical School - Pediatrics
New Brunswick, New Jersey, 08901-1935
Tulane University - Tulane Medical Center - Pediatrics
New Orleans, Louisiana, 70112-2600
Creighton University Medical Center - Medicine - Infectious Diseases
Omaha, Nebraska, 68131-2137
Children's Hospital of Orange County - Infectious Diseases
Orange, California, 92868-3835
Children's Hospital of Pittsburgh of UPMC - Pediatric Infectious Diseases
Pittsburgh, Pennsylvania, 15224-1529
Rhode Island Hospital - Pediatrics
Providence, Rhode Island, 02903-4923
University of Rochester Medical Center - Golisano Children's Hospital - Infectious Diseases
Rochester, New York, 14642-0001
University of Utah - Pediatric Pharmacology Program
Salt Lake City, Utah, 84108-1457
Seattle Children's Hospital - Infectious Diseases
Seattle, Washington, 98105-3901
Louisiana State University Health Shreveport - Pediatrics
Shreveport, Louisiana, 71103-4228
Washington University School of Medicine in St. Louis - Center for Clinical Studies
St Louis, Missouri, 63110-1010
Stanford University School of Medicine
Stanford, California, 94305-2200
SUNY Upstate Medical University Hospital - Pediatrics
Syracuse, New York, 13210-2342
University of South Florida - Tampa General Hospital - Pediatrics
Tampa, Florida, 33606-3438
Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease
Washington D.C., District of Columbia, 20010-2916
United Kingdom7 sites
Birmingham Heartlands Hospital
Birmingham, Birmingham, B9 5SS
Bristol Royal Hospital for Children - UBHT Education Centre
Bristol, Bristol, City of, BS2 8AE
Alder Hey Childrens Hospital
Liverpool, Liverpool, L12 2AP
University College London - Royal Free Campus - Virology
London, London, City of, NW3 2PF
Saint George's Hospital - Pediatric Infectious Diseases
London, London, City of, SW17 0QT
Newcastle General Hospital
Newcastle upon Tyne, Newcastle upon Tyne, NE4 6BE
John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
About this study
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)
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.
Read the 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.
- Conditions
- Cytomegalovirus Infection
- Being tested
- Placebo, Valganciclovir
- Keywords
- Cytomegalovirus, congenital, infants
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
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.
ValganciclovirDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Valganciclovir | Experimental | Six months of oral Valganciclovir. Receives: Drug: Valganciclovir |
| Placebo | Placebo comparator | Six weeks of oral Valganciclovir followed by placebo to complete the six month time period. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Between baseline and 6 months
Secondary outcomes (23)
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.
Measured: baseline through 7 months
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.
Measured: Between baseline and 12 months
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.
Measured: Between baseline and 24 months
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)
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.
Measured: Between baseline and 6 months
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.
Measured: Between baseline and 12 months
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.
Measured: Between baseline and 24 months
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)
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.
Measured: Between baseline and 6 months
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.
Measured: Between baseline and 12 months
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.
Measured: Between baseline and 24 months
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.
Measured: 12 Months after enrollment
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.
Measured: 12 Months after enrollment
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.
Measured: 12 Months after enrollment
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.
Measured: 12 Months after enrollment
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.
Measured: 12 Months after enrollment
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.
Measured: 12 Months after enrollment
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.
Measured: 12 Months after enrollment
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.
Measured: 24 Months after enrollment
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.
Measured: 24 months after enrollment
Neurological Impairment at 24 Months of Life, 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.
Measured: 24 Months after enrollment
Neurologic Impairment at 24 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.
Measured: 24 Months after enrollment
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.
Measured: 24 Months after enrollment
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.
Measured: 24 Months after enrollment.
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.
Measured: 24 Months after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2007 (estimated)
- Study startJun 2008
- Primary completionDec 2011
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00466817
- Sponsor's protocol ID
- 06-0046
- Other IDs
- CASG 112
- Status last verified
- Jul 2015
- First submitted
- 26 Apr 2007
- Last updated
- 26 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 25738669
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00466817
- Acronym / sponsor ID
- 06-0046
- Conditions
- Cytomegalovirus Infection
- Keywords
- Cytomegalovirus, congenital, infants
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jun 2008
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 27 Apr 2007 (estimated)
- Results
- Posted 13 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Valganciclovir | Experimental | Drug: ValganciclovirSix months of oral Valganciclovir. |
| Placebo | Placebo comparator | Other: PlaceboSix weeks of oral Valganciclovir followed by placebo to complete the six month time period. |
Who may qualify
- Ages
- Up to 30 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (13 listed)
- 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:
- Less than or equal to 30 days of age at study enrollment
- Weight at study enrollment greater than or equal to 1800 grams
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo9 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. | Other | Placebo |
| ValganciclovirMono-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. | Drug | Valganciclovir |
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.
23 secondary outcomes
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
Change in Best Ear Hearing Assessments at 12 Months.
Time frame: Between baseline and 12 months
Change in Best Ear Hearing Assessments at 24 Months.
Time frame: Between baseline and 24 months
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
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
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: Between baseline and 24 months
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)
Time frame: Between baseline and 6 months
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)
Time frame: Between baseline and 12 months
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)
Time frame: Between baseline and 24 months
Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Cognitive Composite Score).
Time frame: 12 Months after enrollment
Neurological Impairment at 12 Months of Age Utilizing the Bayley Scales of Infant and Toddler Development (Receptive Communication Scaled Score).
Time frame: 12 Months after enrollment
Neurological Impairment at 12 Months of Age Utilizing the Bayley Scales of Infant and Toddler Development (Expressive Communication Scaled Score).
Time frame: 12 Months after enrollment
Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Language Composite Score).
Time frame: 12 Months after enrollment
Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Fine Motor Scaled Score).
Time frame: 12 Months after enrollment
Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Gross Motor Scaled Score).
Time frame: 12 Months after enrollment
Neurological Impairment at 12 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Motor Composite Score).
Time frame: 12 Months after enrollment
Neurological Impairment at 24 Months Utilizing the Bayley Scales of Infant and Toddler Development (Receptive Communication Scaled Score).
Time frame: 24 Months after enrollment
Neurological Impairment at 24 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Cognitive Composite Score).
Time frame: 24 months after enrollment
Neurological Impairment at 24 Months of Life, Utilizing the Bayley Scales of Infant and Toddler Development (Expressive Communication Scaled Score).
Time frame: 24 Months after enrollment
Neurologic Impairment at 24 Months of Life Utilizing the Bayley Scales of Infant and Toddler Development (Language Composite Score).
Time frame: 24 Months after enrollment
Neurological Impairment at 24 Months, Utilizing the Bayley Scales of Infant and Toddler Development (Fine Motor Scaled Score).
Time frame: 24 Months after enrollment
Neurological Impairment at 24 Months of Life, Utilizing the Bayley Scales of Infant and Toddler Development (Gross Motor Scaled Score).
Time frame: 24 Months after enrollment.
Neurological Impairment at 24 Months of Life, Utilizing the Bayley Scales of Infant and Toddler Development (Motor Composite Score).
Time frame: 24 Months after enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25738669Kimberlin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
48 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Valganciclovir in people with Cytomegalovirus Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 48 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Best Ear Hearing Assessments at 6 Months. (time frame: Between baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00466817, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2015.