Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01376778
Recruitment Status : Completed
First Posted : June 20, 2011
Last Update Posted : September 22, 2021
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The George Washington University Biostatistics Center

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.


Condition or disease Intervention/treatment Phase
Congenital Cytomegalovirus Infection Maternal Cytomegalovirus Infection Drug: CMV hyperimmune globulin Other: Placebo Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 399 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
Study Start Date : April 2012
Actual Primary Completion Date : October 2019
Actual Study Completion Date : June 30, 2021


Arm Intervention/treatment
Active Comparator: CMV hyperimmune globulin - Cytogam®
Infusion of Cytogam®, Cytomegalovirus Immune Globulin Intravenous (Human) (CMV-IGIV)
Drug: CMV hyperimmune globulin
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.
Other Names:
  • CMV-IGIV
  • Cytogam

Placebo Comparator: Placebo
IV 5% albumin diluted 1 to 9 with 5% Dextrose in water (D5W)
Other: Placebo
The matching placebo consists of AlbuRx® 5% diluted 1:9 with D5W. AlbuRx® 5% contains pooled adult human plasma.




Primary Outcome Measures :
  1. Composite Outcome [ Time Frame: 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.


Secondary Outcome Measures :
  1. Gestational hypertension [ Time Frame: from approximately 20 weeks of gestation through delivery (maximum 42 weeks gestation) ]
    Gestational hypertension is a binary outcome defined by occurrence or non-occurrence of gestational hypertension. Gestational hypertension is a new onset hypertension during pregnancy

  2. Preeclampsia [ Time Frame: approximately 20 weeks of gestation through 6 weeks postpartum ]
    Preeclampsia is a binary outcome defined by occurrence or non-occurrence of preeclampsia defined as a patient exhibiting new or worsening hypertension with proteinuria

  3. Placental abruption [ Time Frame: From 16 weeks of gestation through delivery (maximum 42 weeks gestation) ]
    Placental abruption is a binary outcome defined by occurrence or non-occurrence of placental abruption, defined as bleeding and contraction pain

  4. Gestational age at delivery [ Time Frame: Delivery ]
    Gestational age at delivery in weeks and days

  5. Gestational age at delivery before 37 weeks [ Time Frame: Delivery before 37 weeks gestation ]
    Gestational age before 37 weeks gestation is a binary outcome meaning occurrence or non-occurrence of delivery before 37 weeks gestation

  6. Gestational age at delivery before 34 weeks, 0 days [ Time Frame: Delivery before 34 weeks gestation ]
    Gestational age before 34 weeks, 0 days gestation is a binary outcome meaning occurrence or non-occurrence of delivery before 34 weeks gestation

  7. Side effects [ Time Frame: From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation) ]
    Occurrence or non-occurrence of a designated side effect of medication

  8. Treatment emergent severe adverse events [ Time Frame: From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation) ]
    Treatment emergent serious adverse events is a composite binary outcome repeated over time (with the exception of maternal death) and is the occurrence of any one of the following: • Maternal death during the study and while pregnant from any cause related to pregnancy, but not from accidental or incidental causes • Anaphylaxis defined as an acute syndrome occurring within minutes to hours of administration of the study drug and consisting of one or more of the following sets of symptoms: - Angioedema (swelling) of the lips, tongue, uvula and/or throat - Generalized hives, flushing or pruritus accompanied by clinically significant hypotension (usually with tachycardia) - Objective signs of dyspnea such as stridor and/or wheezing • Pulmonary embolism confirmed by spiral CT (or strong suspicion on VQ scan if spiral CT not done) • Deep vein thrombosis confirmed by venogram

  9. Maternal viral load [ Time Frame: From approximately 14-27 weeks gestation through delivery (maximum 42 weeks gestation) ]
    Viral load following the last infusion where viral load is defined as the amount of cytomegalovirus in copies/mL

  10. Fetal mortality [ Time Frame: From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation) ]
    Fetal death

  11. Neonatal mortality [ Time Frame: 0 days to 120 days of life ]
    Death of a neonate that was born alive

  12. Primary outcome excluding terminations [ Time Frame: randomization to 3 weeks postpartum ]
    Occurrence of the primary outcome including spontaneous fetal death but not termination

  13. Neonatal Head circumference [ Time Frame: 72 hours postpartum ]
    Neonatal head circumference measured within 72 hours of birth

  14. Birth weight [ Time Frame: Delivery ]
    Birth weight as recorded in the medical record

  15. Growth restriction [ Time Frame: Delivery ]
    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)

  16. Microcephaly [ Time Frame: Delivery ]
    Microcephaly is a binary outcome defined by the occurrence or non-occurrence of head circumference <3rd percentile for gestational age, assessed specifically by sex of the infant based on Olsen's data from a U.S. population

  17. Symptomatic CMV infection [ Time Frame: During pregnancy up to 3 weeks postpartum ]
    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

  18. Intraventricular hemorrhage [ Time Frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner ]
    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

  19. Ventriculomegaly [ Time Frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner ]
    Ventriculomegaly is a binary outcome defined by the occurrence or non-occurrence of ventriculomegaly

  20. Retinopathy of prematurity (ROP) [ Time Frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner ]
    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.

  21. Respiratory distress syndrome [ Time Frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner ]
    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).

  22. Chronic lung disease [ Time Frame: 28 days of life ]
    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

  23. Necrotizing enterocolitis (NEC) [ Time Frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner ]
    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.

  24. Hyperbilirubinemia [ Time Frame: From birth to 1 week of life ]
    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

  25. Early neonatal sepsis [ Time Frame: 0 days of life to 72 hours of birth ]
    Early neonatal sepsis is a binary outcome defined as the occurrence or non-occurrence of sepsis occurring before 72 hours of birth

  26. Late neonatal sepsis [ Time Frame: Greater than 72 hours of birth to approximately 120 days of life or hospital discharge, whichever is sooner ]
    Late neonatal sepsis is a binary outcome defined as the occurrence or non-occurrence of sepsis occurring late than 72 hours of birth

  27. Suspected neonatal sepsis [ Time Frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner ]
    Suspected neonatal sepsis is a binary outcome defined as the occurrence or non-occurrence of suspected neonatal sepsis

  28. Neonatal pneumonia [ Time Frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner ]
    Neonatal pneumonia is a binary outcome defined as the occurrence or non-occurrence of neonatal pneumonia

  29. Seizures / encephalopathy [ Time Frame: 0 days to approximately 120 days of life or hospital discharge, whichever is sooner ]
    Neonatal seizures/encephalopathy is a binary outcome defined as the occurrence or non-occurrence of seizures/encephalopathy

  30. Neonatal Length of hospital stay [ Time Frame: birth to neonatal hospital discharge (usually a maximum of 120 days) ]
    Length of hospital stay, need for Neonatal Intensive Care Unit (NICU) or intermediate care admission and length of stay if admitted

  31. Infant or child death [ Time Frame: Birth to 24 month study exam ]
    Death of infant or child before the 24 month study exam

  32. Sensorineural hearing loss [ Time Frame: 12 and 24 months corrected age ]
    Sensorineural hearing loss is defined as the occurrence or non-occurrence of sensorineural hearing loss defined as unilateral and bilateral sensorineural hearing loss

  33. Chorioretinitis [ Time Frame: 2 years of age ]
    Chorioretinitis is defined as the occurrence or non-occurrence of chorioetinitis defined by ophthalmologic exam

  34. Cognitive and Motor Scores from the Bayley Certified Scales of Infant Development III [ Time Frame: 12 and 24 months corrected age ]
  35. Infant/Child composite outcome [ Time Frame: 24 month study exam ]
    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

  36. Child status at 24 months of age [ Time Frame: 24 month study exam ]
    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

  37. Failure to thrive [ Time Frame: 12 months and 24 months of age ]
    Failure to thrive defined as <10th percentile for weight at 12 and 24 months

  38. Child viral load [ Time Frame: 12 and 24 months of age ]
    Viral load is defined as the amount of cytomegalovirus in copies/mL



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01376778


Locations
Layout table for location information
United States, Alabama
University of Alabama - Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Stanford, California, United States, 94305-5317
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Case Western Reserve-Metrohealth
Cleveland, Ohio, United States, 44109
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Magee Womens Hospital of UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Brown University
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas - Southwestern Medical Center
Dallas, Texas, United States, 75235
University of Texas - Galveston
Galveston, Texas, United States, 77555
University of Texas - Houston
Houston, Texas, United States, 77030
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
The George Washington University Biostatistics Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Layout table for investigator information
Study Director: Andrew Bremer, M.D., MPH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Rebecca Clifton, PhD George Washington University
Study Chair: Brenna Hughes, MD Brown University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: The George Washington University Biostatistics Center
ClinicalTrials.gov Identifier: NCT01376778    
Other Study ID Numbers: HD36801-CMV
U10HD036801 ( U.S. NIH Grant/Contract )
U10HD027869 ( U.S. NIH Grant/Contract )
U10HD027915 ( U.S. NIH Grant/Contract )
U10HD034116 ( U.S. NIH Grant/Contract )
U10HD034208 ( U.S. NIH Grant/Contract )
U10HD040500 ( U.S. NIH Grant/Contract )
U10HD040485 ( U.S. NIH Grant/Contract )
U10HD040544 ( U.S. NIH Grant/Contract )
U10HD040545 ( U.S. NIH Grant/Contract )
U10HD040560 ( U.S. NIH Grant/Contract )
U10HD040512 ( U.S. NIH Grant/Contract )
U10HD053097 ( U.S. NIH Grant/Contract )
U10HD068282 ( U.S. NIH Grant/Contract )
U10HD068258 ( U.S. NIH Grant/Contract )
U10HD068268 ( U.S. NIH Grant/Contract )
UG1HD087230 ( U.S. NIH Grant/Contract )
UG1HD087192 ( U.S. NIH Grant/Contract )
First Posted: June 20, 2011    Key Record Dates
Last Update Posted: September 22, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Keywords provided by The George Washington University Biostatistics Center:
Perinatology
Cytomegalovirus immune globulin
Cytogam
CMVIG infusions
Additional relevant MeSH terms:
Layout table for MeSH terms
Infections
Communicable Diseases
Cytomegalovirus Infections
Disease Attributes
Pathologic Processes
Herpesviridae Infections
DNA Virus Infections
Virus Diseases