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A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV) (CMV)

Primary Purpose

Congenital Cytomegalovirus Infection, Maternal Cytomegalovirus Infection

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
CMV hyperimmune globulin
Placebo
Sponsored by
The George Washington University Biostatistics Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Congenital Cytomegalovirus Infection focused on measuring Perinatology, Cytomegalovirus immune globulin, Cytogam, CMVIG infusions

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Diagnosis of primary maternal CMV infection on the basis of one of the following:

    1. A positive CMV Immunoglobulin M (IgM) antibody and low-avidity maternal CMV Immunoglobulin G (IgG) antibody screen
    2. Evidence of maternal seroconversion with development of CMV IgG antibody following a prior negative CMV screen
  • Gestational age at randomization no later than 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound; or no later than 27 weeks 6 days for women with a positive IgM, negative IgG initially screened before 23 weeks who are rescreened after 2-4 weeks and have evidence of IgG seroconversion.
  • Singleton pregnancy. A twin pregnancy reduced to singleton (either spontaneously or therapeutically) before 14 weeks by project gestational age is acceptable.

Exclusion Criteria:

  • Maternal CMV infection pre-dating pregnancy as defined by a high IgG avidity index or a positive IgG in the presence of a negative IgM.
  • Known hypersensitivity to plasma or plasma derived products
  • Planned termination of pregnancy
  • Known major fetal anomalies or demise
  • Maternal Immunoglobulin A (IgA) deficiency
  • Planned use of immune globulin, ganciclovir, or valganciclovir
  • Maternal renal disease (most recent pre-randomization serum creatinine ≥ 1.4 mg/dL; all women must have serum creatinine measured during the pregnancy and prior to randomization)
  • Maternal immune impairment (e.g., HIV infection, organ transplant on anti-rejection medications)
  • Findings on pre-randomization ultrasound suggestive of established fetal CMV infection (cerebral ventriculomegaly, microcephaly, cerebral or intra-abdominal calcifications, abnormalities of amniotic fluid volume, echogenic bowel or ascites). Abnormally low amniotic fluid volume is defined as no fluid prior to 14 weeks or maximum vertical pocket < 2 cm on or after 14 weeks gestation. Abnormally high amniotic fluid volume is defined as > 10 cm.
  • Positive fetal CMV findings from culture (amniotic fluid) or PCR.
  • Congenital infection with rubella, syphilis, varicella, parvovirus or toxoplasmosis diagnosed by serology and ultrasound or amniotic fluid testing.
  • Intention of the patient or of the managing obstetricians for the delivery to be outside a Maternal-Fetal Medicine Units Network (MFMU) Network center
  • Participation in another interventional study that influences fetal or neonatal death
  • Unwilling or unable to commit to 2 year follow-up of the infant

Sites / Locations

  • University of Alabama - Birmingham
  • Stanford University
  • University of Colorado Denver
  • Northwestern University
  • Columbia University
  • University of North Carolina - Chapel Hill
  • Duke University
  • Case Western Reserve-Metrohealth
  • Ohio State University
  • Hospital of the University of Pennsylvania
  • Magee Womens Hospital of UPMC
  • Brown University
  • University of Texas - Southwestern Medical Center
  • University of Texas - Galveston
  • University of Texas - Houston
  • University of Utah Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

CMV hyperimmune globulin - Cytogam®

Placebo

Arm Description

Infusion of Cytogam®, Cytomegalovirus Immune Globulin Intravenous (Human) (CMV-IGIV)

IV 5% albumin diluted 1 to 9 with 5% Dextrose in water (D5W)

Outcomes

Primary Outcome Measures

Number of Participants With the Composite Primary Outcome
The primary outcome is a binary outcome defined by the occurrence or non-occurrence of any of the following vs. none of the following: fetal loss (spontaneous or termination), confirmed fetal CMV infection from amniocentesis, neonatal death before assessment of CMV infection can be made, or neonatal congenital CMV infection. Neonatal congenital CMV infection is diagnosed by urine or saliva collected by 3 weeks of age that is positive for CMV by culture (the intent will be to obtain in the first two days of life). In the event that Polymerase Chain Reaction (PCR) is positive but culture is negative, a repeat culture must be positive by 3 weeks of age.
Number of Participants Who Had a Fetus or Neonate With CMV Infection
Component of composite primary outcome
Number of Participants Who Had a Neonatal Death Without CMV Infection
component of composite primary outcome
Number of Participants With a Fetal or Neonatal Death With Proven CMV Infection
component of primary composite outcome
Number of Participants With Fetal Death Without Proven CMV Infection
component of primary composite outcome

Secondary Outcome Measures

Number of Participants With Gestational Hypertension or Preeclampsia
Gestational hypertension or preeclampsia is a binary outcome defined by occurrence or non-occurrence of gestational hypertension or preeclampsia. Gestational hypertension or preeclampsia are new onset hypertension during pregnancy
Number of Participants With Placental Abruption
Placental abruption is a binary outcome defined by occurrence or non-occurrence of placental abruption, defined as bleeding and contraction pain
Median Gestational Age at Delivery
Gestational age at delivery in weeks
Number of Participants Whose Gestational Age at Delivery Was Before 37 Weeks
Gestational age before 37 weeks gestation is a binary outcome meaning occurrence or non-occurrence of delivery before 37 weeks gestation
Number of Participants Whose Gestational Age at Delivery Was Before 34 Weeks, 0 Days
Gestational age before 34 weeks, 0 days gestation is a binary outcome meaning occurrence or non-occurrence of delivery before 34 weeks gestation
Number of Participants Reporting Yes or no to Medication Side Effects
Occurrence or non-occurrence of a designated side effect of medication
Number of Participants Who Had a Fetal or Neonatal Death
Fetal death or death of a neonate born alive
Median Neonatal Head Circumference
Neonatal head circumference measured within 72 hours of birth
Median Birth Weight
Birth weight as recorded in the medical record
Number of Participants With Fetal Growth Restriction
Fetal growth restriction is a binary outcome defined as the occurrence or non-occurrence of growth restriction (defined as <5th percentile weight for gestational age, assessed specifically by sex and race of the infant based on United States birth certificate data)
Number of Participants With Symptomatic CMV Infection
Fetal or neonatal symptomatic CMV infection is a binary outcome defined as the occurrence or non-occurrence of symptomatic CMV infection defined as CMV isolated from an amniocentesis, or urine or saliva during the first three weeks of life and at least one of the following: jaundice (with direct bilirubin exceeding 20% of total bilirubin), thrombocytopenia , anemia , hepatitis, hepatomegaly, splenomegaly, growth restriction, failure to thrive, intracerebral calcifications, microcephaly, hypotonia, seizures, petechial rash, hearing loss, interstitial pneumonitis, thrombocytopenia, anemia, hepatitis, chorioretinitis, or CMV in cerebrospinal fluid
Number of Neonates With Grade 3 or 4 Intraventricular Hemorrhage
Intraventricular hemorrhage (IVH) as determined by cranial ultrasounds performed as part of routine clinical care and classified based on the Papile classification system. IVH is a binary outcome defined by occurrence or non-occurrence of IVH
Number of Neonates With Ventriculomegaly
Ventriculomegaly is a binary outcome defined by the occurrence or non-occurrence of ventriculomegaly
Number of Neonates With Retinopathy of Prematurity (ROP)
Retinopathy of prematurity is a binary outcome defined by the occurrence or non-occurrence of retinopathy of prematurity, diagnosed by ophthalmologic examination of the retina and a diagnosis of Stage I (demarcation line in the retina) or greater.
Number of Neonates With Respiratory Distress Syndrome
Respiratory distress syndrome is a binary outcome defined by the occurrence or non-occurrence of Respiratory distress syndrome (defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with an oxygen requirement and a chest x-ray that shows hypoventilation and reticulogranular infiltrates).
Number of Neonates With Chronic Lung Disease
Neonatal chronic lung disease is a binary outcome defined by the occurrence or non-occurrence of chronic lung disease or bronchopulmonary dysplasia (BPD) defined as oxygen requirement at 28 days of life
Number of Neonates With Necrotizing Enterocolitis (NEC)
Necrotizing enterocolitis (NEC) is a binary outcome defined by the occurrence or non-occurrence of NEC, defined as modified Bell Stage 2 or 3. Stage 2: Clinical signs and symptoms with pneumatosis intestinalis on radiographs. Stage 3: Advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation.
Number of Neonates With Hyperbilirubinemia
Hyperbilirubinemia is a binary outcome defined by the occurrence or non-occurrence of hyperbilirubinemia. Peak total bilirubin of at least 15 mg% or the use of phototherapy
Number of Neonates With Suspected Neonatal Sepsis
Suspected neonatal sepsis is a binary outcome defined as the occurrence or non-occurrence of suspected neonatal sepsis
Number of Neonates With Neonatal Pneumonia
Neonatal pneumonia is a binary outcome defined as the occurrence or non-occurrence of neonatal pneumonia
Number of Neonates Experiencing Seizures / Encephalopathy
Neonatal seizures/encephalopathy is a binary outcome defined as the occurrence or non-occurrence of seizures/encephalopathy
Median Length of Neonatal Hospital Stay
Length of hospital stay, need for Neonatal Intensive Care Unit (NICU) or intermediate care admission and length of stay if admitted
Number of Participants Experiencing Infant or Child Death
Death of infant or child before the 24 month study exam
Number of Children With Sensorineural Hearing Loss
Sensorineural hearing loss is defined as the occurrence or non-occurrence of sensorineural hearing loss defined as unilateral and bilateral sensorineural hearing loss
Number of Children Diagnosed With Chorioretinitis
Chorioretinitis is defined as the occurrence or non-occurrence of chorioretinitis defined by ophthalmologic exam
Mean Cognitive Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)
The Bayley Scales of Infant and Toddler Development® | Third Edition (Bayley®-III), is a comprehensive tool to identify development issues during early childhood. The Bayley-III Cognitive Scale subtests assess cognitive function through the use of memory, problem solving and manipulation subtests. Scores on individual Cognitive subtests range from 1 (worst outcome) to 19 (better outcome) (Mean 10, SD 3). Individual subtest scores between 8 and 12 are considered average. The raw scores on the subtests are converted to scaled scores based on American norms by age. Cognitive Scale composite scores range from 55 (low, worse outcome) to 155 (high, better outcome) (mean 100; SD 15). Severe disability was defined as a composite score <70.
Mean Motor Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)
The Bayley Scales of Infant and Toddler Development® | Third Edition (Bayley®-III), is a comprehensive tool to identify development issues during early childhood. The Bayley-III Motor Scale subtests assess motor function through fine motor and gross motor subtests. Scores on individual Motor subtests range from 1 (worst outcome) to 19 (better outcome) (Mean 10, SD 3). Individual subtest scores between 8 and 12 are considered average. The raw scores on the subtests are converted to scaled scores based on American norms by age. Motor Scale composite scores range from 55 (low, worse outcome) to 155 (high, better outcome) (mean 100; SD 15). Severe disability was defined as a composite score <70.
Number of Infants or Children With the Composite Outcome
Composite outcome at 24 months including any of the following attributable to congenital CMV infection: • Sensorineural hearing loss (unilateral and bilateral) • Developmental delay defined as Cognitive score < 70 or Motor score < 70 on the Bayley III • Chorioretinitis • Fetal loss or death of neonate, infant or child
Overall Child Status at 24 Months of Age
Child status at age 24 months, classified as: • Fetal loss or death of neonate, infant or child • Congenital CMV infection with severe disability • Congenital CMV infection without severe disability • Infant not infected with CMV
Failure to Thrive at 24 Months
Failure to thrive defined as <10th percentile for weight at 24 months

Full Information

First Posted
June 15, 2011
Last Updated
January 17, 2023
Sponsor
The George Washington University Biostatistics Center
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT01376778
Brief Title
A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
Acronym
CMV
Official Title
A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
October 2019 (Actual)
Study Completion Date
June 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The George Washington University Biostatistics Center
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Cytomegalovirus (CMV) is a common virus that usually presents with few if any side effects. When first infected, some people may have symptoms similar to mononucleosis (i.e., fatigue, weakness, fever, swollen glands). Most people in the United States are infected during childhood or as adults if they work around children. Pregnant women, who have not been infected with CMV in the past and become infected during pregnancy (i.e. a primary infection), may cause their babies to get infected with CMV. Babies that are infected may develop permanent disabilities including hearing loss and a small portion will die from the infection. Currently it is not routine practice to screen pregnant women for CMV infection. Additionally, there is no agreement about how to evaluate and manage pregnant women infected with CMV for the first time. There is also no evidence that treatment is beneficial for the baby. The purpose of this research study is to determine whether treating pregnant women who have a primary CMV infection with CMV antibodies will reduce the number of babies infected with CMV.
Detailed Description
Cytomegalovirus (CMV) is the most common congenital infection, with approximately 44,000 congenitally infected infants in the U.S. per year. A substantial proportion of these infants will die or suffer permanent injury as a result of their infection. The severity of congenital infection is greatest with primary maternal CMV infection. Currently, there is no proven method of preventing congenital CMV infection, and the approach to primary maternal CMV infection in the United States is haphazard and ineffective. One small, non-randomized study suggests that maternal administration of CMV hyperimmune globulin may significantly reduce the rate of congenital CMV infection following maternal primary infection. The MFMU CMV Trial will address the primary research question: does maternal administration of CMV hyperimmune globulin lower the rate of congenital CMV infection among the offspring of women who have been diagnosed with primary CMV infection during early pregnancy? The research study is funded by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD). Sixteen medical centers across the country are participating in this research study. In all, 800 pregnant women who are identified with a primary CMV infection will be enrolled in this research study. The children of these women will be evaluated and tested at one and two years of age.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Cytomegalovirus Infection, Maternal Cytomegalovirus Infection
Keywords
Perinatology, Cytomegalovirus immune globulin, Cytogam, CMVIG infusions

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
399 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CMV hyperimmune globulin - Cytogam®
Arm Type
Active Comparator
Arm Description
Infusion of Cytogam®, Cytomegalovirus Immune Globulin Intravenous (Human) (CMV-IGIV)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
IV 5% albumin diluted 1 to 9 with 5% Dextrose in water (D5W)
Intervention Type
Drug
Intervention Name(s)
CMV hyperimmune globulin
Other Intervention Name(s)
CMV-IGIV, Cytogam
Intervention Description
The study's active drug is Cytogam® which is an immunoglobulin G (IgG) containing a standardized amount of antibody to CMV. This drug contains pooled adult human plasma selected for high titers of antibody for CMV, and is administered intravenously at a dose of 100 mg/kg body weight.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
The matching placebo consists of AlbuRx® 5% diluted 1:9 with D5W. AlbuRx® 5% contains pooled adult human plasma.
Primary Outcome Measure Information:
Title
Number of Participants With the Composite Primary Outcome
Description
The primary outcome is a binary outcome defined by the occurrence or non-occurrence of any of the following vs. none of the following: fetal loss (spontaneous or termination), confirmed fetal CMV infection from amniocentesis, neonatal death before assessment of CMV infection can be made, or neonatal congenital CMV infection. Neonatal congenital CMV infection is diagnosed by urine or saliva collected by 3 weeks of age that is positive for CMV by culture (the intent will be to obtain in the first two days of life). In the event that Polymerase Chain Reaction (PCR) is positive but culture is negative, a repeat culture must be positive by 3 weeks of age.
Time Frame
From randomization through 3 weeks of life
Title
Number of Participants Who Had a Fetus or Neonate With CMV Infection
Description
Component of composite primary outcome
Time Frame
From randomization through 3 weeks of life
Title
Number of Participants Who Had a Neonatal Death Without CMV Infection
Description
component of composite primary outcome
Time Frame
From randomization through 3 weeks of life
Title
Number of Participants With a Fetal or Neonatal Death With Proven CMV Infection
Description
component of primary composite outcome
Time Frame
From randomization through 3 weeks of life
Title
Number of Participants With Fetal Death Without Proven CMV Infection
Description
component of primary composite outcome
Time Frame
From randomization through delivery
Secondary Outcome Measure Information:
Title
Number of Participants With Gestational Hypertension or Preeclampsia
Description
Gestational hypertension or preeclampsia is a binary outcome defined by occurrence or non-occurrence of gestational hypertension or preeclampsia. Gestational hypertension or preeclampsia are new onset hypertension during pregnancy
Time Frame
from randomization through discharge from the hospital
Title
Number of Participants With Placental Abruption
Description
Placental abruption is a binary outcome defined by occurrence or non-occurrence of placental abruption, defined as bleeding and contraction pain
Time Frame
From randomization through delivery (maximum 42 weeks gestation)
Title
Median Gestational Age at Delivery
Description
Gestational age at delivery in weeks
Time Frame
Delivery
Title
Number of Participants Whose Gestational Age at Delivery Was Before 37 Weeks
Description
Gestational age before 37 weeks gestation is a binary outcome meaning occurrence or non-occurrence of delivery before 37 weeks gestation
Time Frame
Delivery before 37 weeks gestation
Title
Number of Participants Whose Gestational Age at Delivery Was Before 34 Weeks, 0 Days
Description
Gestational age before 34 weeks, 0 days gestation is a binary outcome meaning occurrence or non-occurrence of delivery before 34 weeks gestation
Time Frame
Delivery before 34 weeks gestation
Title
Number of Participants Reporting Yes or no to Medication Side Effects
Description
Occurrence or non-occurrence of a designated side effect of medication
Time Frame
From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation)
Title
Number of Participants Who Had a Fetal or Neonatal Death
Description
Fetal death or death of a neonate born alive
Time Frame
From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation) up to 120 days of life
Title
Median Neonatal Head Circumference
Description
Neonatal head circumference measured within 72 hours of birth
Time Frame
72 hours postpartum
Title
Median Birth Weight
Description
Birth weight as recorded in the medical record
Time Frame
Delivery
Title
Number of Participants With Fetal Growth Restriction
Description
Fetal growth restriction is a binary outcome defined as the occurrence or non-occurrence of growth restriction (defined as <5th percentile weight for gestational age, assessed specifically by sex and race of the infant based on United States birth certificate data)
Time Frame
Delivery
Title
Number of Participants With Symptomatic CMV Infection
Description
Fetal or neonatal symptomatic CMV infection is a binary outcome defined as the occurrence or non-occurrence of symptomatic CMV infection defined as CMV isolated from an amniocentesis, or urine or saliva during the first three weeks of life and at least one of the following: jaundice (with direct bilirubin exceeding 20% of total bilirubin), thrombocytopenia , anemia , hepatitis, hepatomegaly, splenomegaly, growth restriction, failure to thrive, intracerebral calcifications, microcephaly, hypotonia, seizures, petechial rash, hearing loss, interstitial pneumonitis, thrombocytopenia, anemia, hepatitis, chorioretinitis, or CMV in cerebrospinal fluid
Time Frame
During pregnancy up to 3 weeks postpartum
Title
Number of Neonates With Grade 3 or 4 Intraventricular Hemorrhage
Description
Intraventricular hemorrhage (IVH) as determined by cranial ultrasounds performed as part of routine clinical care and classified based on the Papile classification system. IVH is a binary outcome defined by occurrence or non-occurrence of IVH
Time Frame
0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Title
Number of Neonates With Ventriculomegaly
Description
Ventriculomegaly is a binary outcome defined by the occurrence or non-occurrence of ventriculomegaly
Time Frame
0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Title
Number of Neonates With Retinopathy of Prematurity (ROP)
Description
Retinopathy of prematurity is a binary outcome defined by the occurrence or non-occurrence of retinopathy of prematurity, diagnosed by ophthalmologic examination of the retina and a diagnosis of Stage I (demarcation line in the retina) or greater.
Time Frame
0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Title
Number of Neonates With Respiratory Distress Syndrome
Description
Respiratory distress syndrome is a binary outcome defined by the occurrence or non-occurrence of Respiratory distress syndrome (defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with an oxygen requirement and a chest x-ray that shows hypoventilation and reticulogranular infiltrates).
Time Frame
0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Title
Number of Neonates With Chronic Lung Disease
Description
Neonatal chronic lung disease is a binary outcome defined by the occurrence or non-occurrence of chronic lung disease or bronchopulmonary dysplasia (BPD) defined as oxygen requirement at 28 days of life
Time Frame
28 days of life
Title
Number of Neonates With Necrotizing Enterocolitis (NEC)
Description
Necrotizing enterocolitis (NEC) is a binary outcome defined by the occurrence or non-occurrence of NEC, defined as modified Bell Stage 2 or 3. Stage 2: Clinical signs and symptoms with pneumatosis intestinalis on radiographs. Stage 3: Advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation.
Time Frame
0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Title
Number of Neonates With Hyperbilirubinemia
Description
Hyperbilirubinemia is a binary outcome defined by the occurrence or non-occurrence of hyperbilirubinemia. Peak total bilirubin of at least 15 mg% or the use of phototherapy
Time Frame
From birth to 1 week of life
Title
Number of Neonates With Suspected Neonatal Sepsis
Description
Suspected neonatal sepsis is a binary outcome defined as the occurrence or non-occurrence of suspected neonatal sepsis
Time Frame
0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Title
Number of Neonates With Neonatal Pneumonia
Description
Neonatal pneumonia is a binary outcome defined as the occurrence or non-occurrence of neonatal pneumonia
Time Frame
0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Title
Number of Neonates Experiencing Seizures / Encephalopathy
Description
Neonatal seizures/encephalopathy is a binary outcome defined as the occurrence or non-occurrence of seizures/encephalopathy
Time Frame
0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Title
Median Length of Neonatal Hospital Stay
Description
Length of hospital stay, need for Neonatal Intensive Care Unit (NICU) or intermediate care admission and length of stay if admitted
Time Frame
birth to neonatal hospital discharge (usually a maximum of 120 days)
Title
Number of Participants Experiencing Infant or Child Death
Description
Death of infant or child before the 24 month study exam
Time Frame
Birth to 24 month study exam
Title
Number of Children With Sensorineural Hearing Loss
Description
Sensorineural hearing loss is defined as the occurrence or non-occurrence of sensorineural hearing loss defined as unilateral and bilateral sensorineural hearing loss
Time Frame
12 and 24 months corrected age
Title
Number of Children Diagnosed With Chorioretinitis
Description
Chorioretinitis is defined as the occurrence or non-occurrence of chorioretinitis defined by ophthalmologic exam
Time Frame
2 years of age
Title
Mean Cognitive Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)
Description
The Bayley Scales of Infant and Toddler Development® | Third Edition (Bayley®-III), is a comprehensive tool to identify development issues during early childhood. The Bayley-III Cognitive Scale subtests assess cognitive function through the use of memory, problem solving and manipulation subtests. Scores on individual Cognitive subtests range from 1 (worst outcome) to 19 (better outcome) (Mean 10, SD 3). Individual subtest scores between 8 and 12 are considered average. The raw scores on the subtests are converted to scaled scores based on American norms by age. Cognitive Scale composite scores range from 55 (low, worse outcome) to 155 (high, better outcome) (mean 100; SD 15). Severe disability was defined as a composite score <70.
Time Frame
12 and 24 months corrected age
Title
Mean Motor Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)
Description
The Bayley Scales of Infant and Toddler Development® | Third Edition (Bayley®-III), is a comprehensive tool to identify development issues during early childhood. The Bayley-III Motor Scale subtests assess motor function through fine motor and gross motor subtests. Scores on individual Motor subtests range from 1 (worst outcome) to 19 (better outcome) (Mean 10, SD 3). Individual subtest scores between 8 and 12 are considered average. The raw scores on the subtests are converted to scaled scores based on American norms by age. Motor Scale composite scores range from 55 (low, worse outcome) to 155 (high, better outcome) (mean 100; SD 15). Severe disability was defined as a composite score <70.
Time Frame
12 and 24 months corrected age
Title
Number of Infants or Children With the Composite Outcome
Description
Composite outcome at 24 months including any of the following attributable to congenital CMV infection: • Sensorineural hearing loss (unilateral and bilateral) • Developmental delay defined as Cognitive score < 70 or Motor score < 70 on the Bayley III • Chorioretinitis • Fetal loss or death of neonate, infant or child
Time Frame
24 month study exam
Title
Overall Child Status at 24 Months of Age
Description
Child status at age 24 months, classified as: • Fetal loss or death of neonate, infant or child • Congenital CMV infection with severe disability • Congenital CMV infection without severe disability • Infant not infected with CMV
Time Frame
24 month study exam
Title
Failure to Thrive at 24 Months
Description
Failure to thrive defined as <10th percentile for weight at 24 months
Time Frame
24 months of age

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Diagnosis of primary maternal CMV infection on the basis of one of the following: A positive CMV Immunoglobulin M (IgM) antibody and low-avidity maternal CMV Immunoglobulin G (IgG) antibody screen Evidence of maternal seroconversion with development of CMV IgG antibody following a prior negative CMV screen Gestational age at randomization no later than 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound; or no later than 27 weeks 6 days for women with a positive IgM, negative IgG initially screened before 23 weeks who are rescreened after 2-4 weeks and have evidence of IgG seroconversion. Singleton pregnancy. A twin pregnancy reduced to singleton (either spontaneously or therapeutically) before 14 weeks by project gestational age is acceptable. Exclusion Criteria: Maternal CMV infection pre-dating pregnancy as defined by a high IgG avidity index or a positive IgG in the presence of a negative IgM. Known hypersensitivity to plasma or plasma derived products Planned termination of pregnancy Known major fetal anomalies or demise Maternal Immunoglobulin A (IgA) deficiency Planned use of immune globulin, ganciclovir, or valganciclovir Maternal renal disease (most recent pre-randomization serum creatinine ≥ 1.4 mg/dL; all women must have serum creatinine measured during the pregnancy and prior to randomization) Maternal immune impairment (e.g., HIV infection, organ transplant on anti-rejection medications) Findings on pre-randomization ultrasound suggestive of established fetal CMV infection (cerebral ventriculomegaly, microcephaly, cerebral or intra-abdominal calcifications, abnormalities of amniotic fluid volume, echogenic bowel or ascites). Abnormally low amniotic fluid volume is defined as no fluid prior to 14 weeks or maximum vertical pocket < 2 cm on or after 14 weeks gestation. Abnormally high amniotic fluid volume is defined as > 10 cm. Positive fetal CMV findings from culture (amniotic fluid) or PCR. Congenital infection with rubella, syphilis, varicella, parvovirus or toxoplasmosis diagnosed by serology and ultrasound or amniotic fluid testing. Intention of the patient or of the managing obstetricians for the delivery to be outside a Maternal-Fetal Medicine Units Network (MFMU) Network center Participation in another interventional study that influences fetal or neonatal death Unwilling or unable to commit to 2 year follow-up of the infant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Monica Longo, MD
Organizational Affiliation
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Rebecca Clifton, PhD
Organizational Affiliation
George Washington University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Brenna Hughes, MD
Organizational Affiliation
Brown University
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama - Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5317
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of North Carolina - Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Case Western Reserve-Metrohealth
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Magee Womens Hospital of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Brown University
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
University of Texas - Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Texas - Galveston
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States
Facility Name
University of Texas - Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The dataset will be shared per NIH policy after the completion and publication of the main analyses. Requests for datasets can be sent to mfmudatasets@bsc.gwu.edu.
Citations:
PubMed Identifier
34320288
Citation
Hughes BL, Clifton RG, Rouse DJ, Saade GR, Dinsmoor MJ, Reddy UM, Pass R, Allard D, Mallett G, Fette LM, Gyamfi-Bannerman C, Varner MW, Goodnight WH, Tita ATN, Costantine MM, Swamy GK, Gibbs RS, Chien EK, Chauhan SP, El-Sayed YY, Casey BM, Parry S, Simhan HN, Napolitano PG, Macones GA; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection. N Engl J Med. 2021 Jul 29;385(5):436-444. doi: 10.1056/NEJMoa1913569.
Results Reference
result
PubMed Identifier
35115450
Citation
Rouse DJ, Fette LM, Hughes BL, Saade GR, Dinsmoor MJ, Reddy UM, Pass R, Allard D, Mallett G, Clifton RG, Saccoccio FM, Permar SR, Gyamfi-Bannerman C, Varner MW, Goodnight WH, Tita ATN, Costantine MM, Swamy GK, Heyborne KD, Chien EK, Chauhan SP, El-Sayed YY, Casey BM, Parry S, Simhan HN, Napolitano PG, Macones GA; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Noninvasive Prediction of Congenital Cytomegalovirus Infection After Maternal Primary Infection. Obstet Gynecol. 2022 Mar 1;139(3):400-406. doi: 10.1097/AOG.0000000000004691.
Results Reference
result
PubMed Identifier
35526782
Citation
Dinsmoor MJ, Fette LM, Hughes BL, Rouse DJ, Saade GR, Reddy UM, Allard D, Mallett G, Thom EA, Gyamfi-Bannerman C, Varner MW, Goodnight WH, Tita ATN, Costantine MM, Swamy GK, Heyborne KD, Chien EK, Chauhan SP, El-Sayed YY, Casey BM, Parry S, Simhan HN, Napolitano PG, Macones GA; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. Amniocentesis to diagnose congenital cytomegalovirus infection following maternal primary infection. Am J Obstet Gynecol MFM. 2022 Jul;4(4):100641. doi: 10.1016/j.ajogmf.2022.100641. Epub 2022 May 6.
Results Reference
derived

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A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)

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