Congenital Cytomegalovirus InfectionPhase 3CMVNCT01376778
A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
A Phase 3 study testing CMV hyperimmune globulin in people with Congenital Cytomegalovirus Infection and Maternal Cytomegalovirus Infection, run by The George Washington University Biostatistics Center at 16 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Congenital Cytomegalovirus Infection, Maternal Cytomegalovirus Infection
- What is being tested?
- CMV hyperimmune globulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 399 participants
- Where
- 16 sitesUnited States
- Study dates
- Apr 2012to 30 Jun 2021
- 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 Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
University of Colorado Denver
Aurora, Colorado, 80045
University of Alabama - Birmingham
Birmingham, Alabama, 35233
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599
Northwestern University
Chicago, Illinois, 60611
Case Western Reserve-Metrohealth
Cleveland, Ohio, 44109
Ohio State University
Columbus, Ohio, 43210
University of Texas - Southwestern Medical Center
Dallas, Texas, 75235
Duke University
Durham, North Carolina, 27710
University of Texas - Galveston
Galveston, Texas, 77555
University of Texas - Houston
Houston, Texas, 77030
Columbia University
New York, New York, 10032
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Magee Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
Brown University
Providence, Rhode Island, 02905
University of Utah Medical Center
Salt Lake City, Utah, 84132
Stanford University
Stanford, California, 94305-5317
About this study
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.
Read the 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.
- Being tested
- CMV hyperimmune globulin, Placebo
- Keywords
- Perinatology, Cytomegalovirus immune globulin, Cytogam, CMVIG infusions
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV hyperimmune globulinDrug
Also called CMV-IGIV, Cytogam
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.
PlaceboOther
The matching placebo consists of AlbuRx® 5% diluted 1:9 with D5W. AlbuRx® 5% contains pooled adult human plasma.
| Study group | Role | What they receive |
|---|---|---|
| CMV hyperimmune globulin - Cytogam® | Active comparator | Infusion of Cytogam®, Cytomegalovirus Immune Globulin Intravenous (Human) (CMV-IGIV) Receives: Drug: CMV hyperimmune globulin |
| Placebo | Placebo comparator | IV 5% albumin diluted 1 to 9 with 5% Dextrose in water (D5W) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization through 3 weeks of life
Number of Participants Who Had a Fetus or Neonate With CMV Infection
Component of composite primary outcome
Measured: From randomization through 3 weeks of life
Number of Participants Who Had a Neonatal Death Without CMV Infection
component of composite primary outcome
Measured: From randomization through 3 weeks of life
Number of Participants With a Fetal or Neonatal Death With Proven CMV Infection
component of primary composite outcome
Measured: From randomization through 3 weeks of life
Number of Participants With Fetal Death Without Proven CMV Infection
component of primary composite outcome
Measured: From randomization through delivery
Secondary outcomes (30)
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
Measured: from randomization through discharge from the hospital
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
Measured: From randomization through delivery (maximum 42 weeks gestation)
Median Gestational Age at Delivery
Gestational age at delivery in weeks
Measured: Delivery
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
Measured: 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
Measured: 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
Measured: From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation)
Number of Participants Who Had a Fetal or Neonatal Death
Fetal death or death of a neonate born alive
Measured: From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation) up to 120 days of life
Median Neonatal Head Circumference
Neonatal head circumference measured within 72 hours of birth
Measured: 72 hours postpartum
Median Birth Weight
Birth weight as recorded in the medical record
Measured: Delivery
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)
Measured: Delivery
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
Measured: During pregnancy up to 3 weeks postpartum
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
Measured: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates With Ventriculomegaly
Ventriculomegaly is a binary outcome defined by the occurrence or non-occurrence of ventriculomegaly
Measured: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
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.
Measured: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
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).
Measured: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
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
Measured: 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.
Measured: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
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
Measured: From birth to 1 week of life
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
Measured: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates With Neonatal Pneumonia
Neonatal pneumonia is a binary outcome defined as the occurrence or non-occurrence of neonatal pneumonia
Measured: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates Experiencing Seizures / Encephalopathy
Neonatal seizures/encephalopathy is a binary outcome defined as the occurrence or non-occurrence of seizures/encephalopathy
Measured: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
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
Measured: birth to neonatal hospital discharge (usually a maximum of 120 days)
Number of Participants Experiencing Infant or Child Death
Death of infant or child before the 24 month study exam
Measured: Birth to 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
Measured: 12 and 24 months corrected age
Number of Children Diagnosed With Chorioretinitis
Chorioretinitis is defined as the occurrence or non-occurrence of chorioretinitis defined by ophthalmologic exam
Measured: 2 years of age
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.
Measured: 12 and 24 months corrected age
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.
Measured: 12 and 24 months corrected age
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
Measured: 24 month study exam
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
Measured: 24 month study exam
Failure to Thrive at 24 Months
Failure to thrive defined as <10th percentile for weight at 24 months
Measured: 24 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2011 (estimated)
- Study startApr 2012
- Primary completionOct 2019
- Study completion30 Jun 2021
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 (3)Papers the sponsor has linked to this study.
- Other trials for Congenital Cytomegalovirus InfectionStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 399 participants (actual)
Sponsor and investigators
- Lead sponsor
- The George Washington University Biostatistics Center
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Monica Longo, MD, Study director, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Rebecca Clifton, PhD, Principal investigator, George Washington UniversityBrenna Hughes, MD, Study chair, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01376778
- Sponsor's protocol ID
- HD36801-CMV
- Other IDs
- U10HD036801, U10HD027869, U10HD027915, U10HD034116, U10HD034208, U10HD040500, U10HD040485, U10HD040544
- Acronym
- CMV
- Status last verified
- Jan 2023
- First submitted
- 15 Jun 2011
- Last updated
- 2 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 34320288Rouse 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.
PubMed 35115450Dinsmoor 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.
PubMed 35526782
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
- ClinicalTrials.gov ID
- NCT01376778
- Acronym / sponsor ID
- CMV / HD36801-CMV
- Keywords
- Perinatology, Cytomegalovirus immune globulin, Cytogam, CMVIG infusions
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 399 participants (actual)
- Lead sponsor
- The George Washington University Biostatistics CenterUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Apr 2012
- Primary completion
- Oct 2019 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 20 Jun 2011 (estimated)
- Results
- Posted 2 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CMV hyperimmune globulin - Cytogam® | Active comparator | Drug: CMV hyperimmune globulinInfusion of Cytogam®, Cytomegalovirus Immune Globulin Intravenous (Human) (CMV-IGIV) |
| Placebo | Placebo comparator | Other: PlaceboIV 5% albumin diluted 1 to 9 with 5% Dextrose in water (D5W) |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of primary maternal CMV infection on the basis of one of the following:
- 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.
Key exclusion criteria (14 listed)
- 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
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 |
|---|---|---|
| CMV hyperimmune globulinAlso: CMV-IGIV, CytogamThe 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. | Drug | CMV hyperimmune globulin - Cytogam® |
| PlaceboThe matching placebo consists of AlbuRx® 5% diluted 1:9 with D5W. AlbuRx® 5% contains pooled adult human plasma. | Other | Placebo |
Primary outcome
Number of Participants With the Composite Primary Outcome
Time frame: From randomization through 3 weeks of life
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
Time frame: From randomization through 3 weeks of life
Component of composite primary outcome
Number of Participants Who Had a Neonatal Death Without CMV Infection
Time frame: From randomization through 3 weeks of life
component of composite primary outcome
Number of Participants With a Fetal or Neonatal Death With Proven CMV Infection
Time frame: From randomization through 3 weeks of life
component of primary composite outcome
Number of Participants With Fetal Death Without Proven CMV Infection
Time frame: From randomization through delivery
component of primary composite outcome
30 secondary outcomes
Number of Participants With Gestational Hypertension or Preeclampsia
Time frame: from randomization through discharge from the hospital
Number of Participants With Placental Abruption
Time frame: From randomization through delivery (maximum 42 weeks gestation)
Median Gestational Age at Delivery
Time frame: Delivery
Number of Participants Whose Gestational Age at Delivery Was Before 37 Weeks
Time frame: Delivery before 37 weeks gestation
Number of Participants Whose Gestational Age at Delivery Was Before 34 Weeks, 0 Days
Time frame: Delivery before 34 weeks gestation
Number of Participants Reporting Yes or no to Medication Side Effects
Time frame: From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation)
Number of Participants Who Had a Fetal or Neonatal Death
Time frame: From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation) up to 120 days of life
Median Neonatal Head Circumference
Time frame: 72 hours postpartum
Median Birth Weight
Time frame: Delivery
Number of Participants With Fetal Growth Restriction
Time frame: Delivery
Number of Participants With Symptomatic CMV Infection
Time frame: During pregnancy up to 3 weeks postpartum
Number of Neonates With Grade 3 or 4 Intraventricular Hemorrhage
Time frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates With Ventriculomegaly
Time frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates With Retinopathy of Prematurity (ROP)
Time frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates With Respiratory Distress Syndrome
Time frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates With Chronic Lung Disease
Time frame: 28 days of life
Number of Neonates With Necrotizing Enterocolitis (NEC)
Time frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates With Hyperbilirubinemia
Time frame: From birth to 1 week of life
Number of Neonates With Suspected Neonatal Sepsis
Time frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates With Neonatal Pneumonia
Time frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Number of Neonates Experiencing Seizures / Encephalopathy
Time frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner
Median Length of Neonatal Hospital Stay
Time frame: birth to neonatal hospital discharge (usually a maximum of 120 days)
Number of Participants Experiencing Infant or Child Death
Time frame: Birth to 24 month study exam
Number of Children With Sensorineural Hearing Loss
Time frame: 12 and 24 months corrected age
Number of Children Diagnosed With Chorioretinitis
Time frame: 2 years of age
Mean Cognitive Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)
Time frame: 12 and 24 months corrected age
Mean Motor Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)
Time frame: 12 and 24 months corrected age
Number of Infants or Children With the Composite Outcome
Time frame: 24 month study exam
Overall Child Status at 24 Months of Age
Time frame: 24 month study exam
Failure to Thrive at 24 Months
Time frame: 24 months of age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34320288Hughes 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 publication: PubMed 35115450Rouse 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.
- Derived from this study: PubMed 35526782Dinsmoor 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.
- Individual participant dataSharing planned: Yes. 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.
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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.
Monica Longo, MD study director
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Rebecca Clifton, PhD principal investigator
George Washington University
Brenna Hughes, MD study chair
Brown University
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CMV hyperimmune globulin in people with Congenital Cytomegalovirus Infection and Maternal Cytomegalovirus Infection, run by The George Washington University Biostatistics Center at 16 sites in United States.
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 5 inclusion and 14 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 2 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. 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 2 Feb 2023). 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?
Number of Participants With the Composite Primary Outcome (time frame: From randomization through 3 weeks of life). The study lists 5 primary outcomes in all. 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 NCT01376778, which also lists 3 linked publications.
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 2 Feb 2023.