A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
Information source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Congenital Cytomegalovirus Infection; Maternal Cytomegalovirus Infection
Intervention: CMV hyperimmune globulin (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Official(s) and/or principal investigator(s): Uma Reddy, MD, MPH, Study Director, Affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Elizabeth Thom, PhD, Principal Investigator, Affiliation: George Washington University Brenna Anderson, MD, Study Chair, Affiliation: Brown University
Overall contact: Uma Reddy, MD, MPH, Phone: 301-496-1074, Email: Uma.Reddy@nih.gov
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.
Clinical Details
Official title: A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Primary outcome: Composite Outcome
Secondary outcome: Gestational hypertensionPreeclampsia Placental abruption Gestational age at delivery Adverse reactions and side effects Fetal and neonatal mortality Primary outcome excluding terminations Head circumference Birth weight Growth restriction Microcephaly Symptomatic CMV infection Intraventricular hemorrhage Ventriculomegaly Retinopathy of prematurity (ROP) Respiratory distress syndrome Chronic lung disease Necrotizing enterocolitis (NEC) Hyperbilirubinemia Neonatal infectious morbidity Seizures / encephalopathy Length of hospital stay Infant or child death Sensorineural hearing loss Chorioretinitis Cognitive and Motor Scores from the Bayley Certified Scales of Infant Development III Infant/Child composite outcome
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). Fourteen 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.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Female.
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
Locations and Contacts
Uma Reddy, MD, MPH, Phone: 301-496-1074, Email: Uma.Reddy@nih.gov
University of Alabama - Birmingham, Birmingham, Alabama 35233, United States; Recruiting Stacy Harris, BSN, Phone: 205-996-6262, Email: stacylharris@uabmc.edu Alan T Tita, MD, Principal Investigator
Stanford University, Stanford, California 94305-5317, United States; Recruiting Cynthia Willson, RN, BSN, Phone: 650-724-6372, Email: cwillson@stanford.edu Yasser El-Sayed, MD, Principal Investigator
University of Colorado Denver, Aurora, Colorado 80045, United States; Recruiting Kathy Hale, BSN, Phone: 303-724-6685, Email: Kathy.A.Hale@ucdenver.edu Ronald Gibbs, MD, Principal Investigator
Northwestern University, Chicago, Illinois 60611, United States; Recruiting Gail Mallett, BSN, Phone: 312-503-3200, Email: g-mallett@northwestern.edu William Grobman, MD, Principal Investigator
Columbia University, New York, New York 10032, United States; Recruiting Sabine Bousleiman, Phone: 212-305-4348, Email: sb1080@columbia.edu Ronald Wapner, MD, Principal Investigator
University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599, United States; Recruiting Kelly Clark, RN, Phone: 919-350-6117, Email: kelly_clark@med.unc.edu John M Thorp, Jr., MD, Principal Investigator
Duke University, Durham, North Carolina 27710, United States; Recruiting Tammy Sinclair Bishop, RN, Phone: 919-668-7475, Email: sincl008@mc.duke.edu Geeta Swamy, MD, Principal Investigator
Case Western Reserve-Metrohealth, Cleveland, Ohio 44109, United States; Recruiting Wendy Dalton, RN, Phone: 216-778-7533, Email: wdalton@metrohealth.org Edward Chien, MD, Principal Investigator
Ohio State University, Columbus, Ohio 43210, United States; Recruiting Francee Johnson, RN, Phone: 614-293-5632, Email: johnson.126@osu.edu Jay Iams, MD, Principal Investigator
Brown University, Providence, Rhode Island 02905, United States; Recruiting Donna Allard, RNC, Phone: 401-274-1122, Ext: 8522, Email: dallard@wihri.org Dwight Rouse, MD, Principal Investigator
University of Texas - Southwestern Medical Center, Dallas, Texas 75235, United States; Recruiting Lisa Moseley, RN, Phone: 214-648-2591, Email: lisa.moseley@utsouthwestern.edu Brian Casey, MD, Principal Investigator
University of Texas - Galveston, Galveston, Texas 77555, United States; Recruiting Ashley Salazar, MSN, Phone: 409-747-1733, Email: assalaza@utmb.edu George R Saade, MD, Principal Investigator
University of Texas - Houston, Houston, Texas 77030, United States; Recruiting Felecia Ortiz, RN, Phone: 713-500-6467, Email: Felecia.Ortiz@uth.tmc.edu Baha Sibai, MD, Principal Investigator
University of Utah Medical Center, Salt Lake City, Utah 84132, United States; Recruiting Kim Hill, RN, Phone: 801-585-7645, Email: Kim.Hill@hsc.utah.edu Michael W Varner, MD, Principal Investigator
Additional Information
Starting date: April 2012
Last updated: October 28, 2014
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