A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)

NCT01376778 | Completed Phase 3 Results DMC

• 18 other identifiers: HD36801-CMVU10HD036801U10HD027869U10HD027915U10HD034116U10HD034208U10HD040500U10HD040485U10HD040544U10HD040545U10HD040560U10HD040512U10HD053097U10HD068282U10HD068258U10HD068268UG1HD087230UG1HD087192
• Study Type: interventional
• Target: 399
• Locations: 1 country
• Sites: 16

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.

Conditions

Congenital Cytomegalovirus Infection; Maternal Cytomegalovirus Infection

Keywords

Perinatology; Cytomegalovirus immune globulin; Cytogam; CMVIG infusions

Outcome Measures

Primary Outcomes (5)

• 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.

  From randomization through 3 weeks of life

• Number of Participants Who Had a Fetus or Neonate With CMV Infection

  Component of composite primary outcome

  From randomization through 3 weeks of life

• Number of Participants Who Had a Neonatal Death Without CMV Infection

  component of composite primary outcome

  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

  From randomization through 3 weeks of life

• Number of Participants With Fetal Death Without Proven CMV Infection

  component of primary composite outcome

  From randomization through delivery

Secondary Outcomes (30)

• Number of Participants With Gestational Hypertension or Preeclampsia

  from randomization through discharge from the hospital

• Number of Participants With Placental Abruption

  From randomization through delivery (maximum 42 weeks gestation)

• Median Gestational Age at Delivery

  Delivery

• Number of Participants Whose Gestational Age at Delivery Was Before 37 Weeks

  Delivery before 37 weeks gestation

• Number of Participants Whose Gestational Age at Delivery Was Before 34 Weeks, 0 Days

  Delivery before 34 weeks gestation

Study Arms (2)

CMV hyperimmune globulin - Cytogam®

ACTIVE COMPARATOR

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

Drug: CMV hyperimmune globulin

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

CMV hyperimmune globulin 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.

Also known as: CMV-IGIV, Cytogam

CMV hyperimmune globulin - Cytogam®

Placebo OTHER

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

Placebo

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The George Washington University Biostatistics Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (16)

University of Alabama - Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Stanford, California, 94305-5317, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Case Western Reserve-Metrohealth

Cleveland, Ohio, 44109, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Magee Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Brown University

Providence, Rhode Island, 02905, United States

Location

University of Texas - Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

University of Texas - Galveston

Galveston, Texas, 77555, United States

Location

University of Texas - Houston

Houston, Texas, 77030, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

Related Publications (3)

• 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.

  PMID: 34320288 RESULT

• 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.

  PMID: 35115450 RESULT

• 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.

  PMID: 35526782 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

cytomegalovirus-specific hyperimmune globulin

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Dr. Rebecca Clifton, MFMU Principal Investigator
• Organization: The George Washington University Biostatistics Center

rclifton@bsc.gwu.edu

301-881-9260

Study Officials

• Monica Longo, MD

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

  STUDY DIRECTOR

• Rebecca Clifton, PhD

  George Washington University

  PRINCIPAL INVESTIGATOR

• Brenna Hughes, MD

  Brown University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2011
• First Posted: June 20, 2011
• Study Start: April 1, 2012
• Primary Completion: October 1, 2019
• Study Completion: June 30, 2021
• Last Updated: February 2, 2023
• Results First Posted: February 2, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (16)