A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)

NCT ID: NCT01376778

Last Updated: 2023-02-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

399 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-04-30

Study Completion Date

2021-06-30

Brief Summary

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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

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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.

Conditions

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Congenital Cytomegalovirus Infection Maternal Cytomegalovirus Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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CMV hyperimmune globulin - Cytogam®

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

Group Type ACTIVE_COMPARATOR

CMV hyperimmune globulin

Intervention Type DRUG

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.

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

The matching placebo consists of AlbuRx® 5% diluted 1:9 with D5W. AlbuRx® 5% contains pooled adult human plasma.

Interventions

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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.

Intervention Type DRUG

Placebo

The matching placebo consists of AlbuRx® 5% diluted 1:9 with D5W. AlbuRx® 5% contains pooled adult human plasma.

Intervention Type OTHER

Other Intervention Names

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CMV-IGIV Cytogam

Eligibility Criteria

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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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

The George Washington University Biostatistics Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Monica Longo, MD

Role: STUDY_DIRECTOR

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Rebecca Clifton, PhD

Role: PRINCIPAL_INVESTIGATOR

George Washington University

Brenna Hughes, MD

Role: STUDY_CHAIR

Brown University

Locations

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University of Alabama - Birmingham

Birmingham, Alabama, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Columbia University

New York, New York, United States

Site Status

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Case Western Reserve-Metrohealth

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Magee Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Brown University

Providence, Rhode Island, United States

Site Status

University of Texas - Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Texas - Galveston

Galveston, Texas, United States

Site Status

University of Texas - Houston

Houston, Texas, United States

Site Status

University of Utah Medical Center

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 34320288 (View on PubMed)

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.

Reference Type RESULT
PMID: 35115450 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35526782 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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U10HD036801

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD027869

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD027915

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD034116

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD034208

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040500

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040544

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040545

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040560

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040512

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD053097

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD068282

Identifier Type: NIH

Identifier Source: secondary_id

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U10HD068258

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD068268

Identifier Type: NIH

Identifier Source: secondary_id

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UG1HD087230

Identifier Type: NIH

Identifier Source: secondary_id

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UG1HD087192

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HD36801-CMV

Identifier Type: -

Identifier Source: org_study_id

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