Phase 3
N=399
A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
Congenital Cytomegalovirus Infection · Maternal Cytomegalovirus Infection
Bottom Line
View on ClinicalTrials.gov: NCT01376778 ↗Enrolled (actual)
399
Serious AEs
14.3%
Results posted
Feb 2023
Primary outcome: Primary: Number of Participants With the Composite Primary Outcome — 46; 37 Participants — p=0.42
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- CMV hyperimmune globulin (Drug); Placebo (Other)
- Age
- Pediatric, Adult, Older Adult
- Sex
- Female
- Sponsor
- The George Washington University Biostatistics Center
- Primary completion
- Oct 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With the Composite Primary Outcome |
46; 37 | 0.42 |
| PRIMARY Number of Participants Who Had a Fetus or Neonate With CMV Infection |
36; 32 | — |
| PRIMARY Number of Participants Who Had a Neonatal Death Without CMV Infection |
0; 0 | — |
| PRIMARY Number of Participants With a Fetal or Neonatal Death With Proven CMV Infection |
7; 3 | — |
| PRIMARY Number of Participants With Fetal Death Without Proven CMV Infection |
3; 2 | — |
| SECONDARY Number of Participants With Gestational Hypertension or Preeclampsia |
24; 14 | — |
| SECONDARY Number of Participants With Placental Abruption |
3; 1 | — |
| SECONDARY Median Gestational Age at Delivery |
38.2; 38.6 | — |
| SECONDARY Number of Participants Whose Gestational Age at Delivery Was Before 37 Weeks |
25; 16 | — |
| SECONDARY Number of Participants Whose Gestational Age at Delivery Was Before 34 Weeks, 0 Days |
12; 7 | — |
| SECONDARY Number of Participants Reporting Yes or no to Medication Side Effects |
125; 131; 81; 62 | — |
| SECONDARY Number of Participants Who Had a Fetal or Neonatal Death |
10; 5 | — |
| SECONDARY Median Neonatal Head Circumference |
33.9; 34.1 | — |
| SECONDARY Median Birth Weight |
3268; 3303 | — |
| SECONDARY Number of Participants With Fetal Growth Restriction |
20; 10 | — |
| SECONDARY Number of Participants With Symptomatic CMV Infection |
23; 15 | — |
| SECONDARY Number of Neonates With Grade 3 or 4 Intraventricular Hemorrhage |
1; 0 | — |
| SECONDARY Number of Neonates With Ventriculomegaly |
1; 0 | — |
| SECONDARY Number of Neonates With Retinopathy of Prematurity (ROP) |
1; 1 | — |
| SECONDARY Number of Neonates With Respiratory Distress Syndrome |
5; 10 | — |
| SECONDARY Number of Neonates With Chronic Lung Disease |
0; 0 | — |
| SECONDARY Number of Neonates With Necrotizing Enterocolitis (NEC) |
0; 0 | — |
| SECONDARY Number of Neonates With Hyperbilirubinemia |
13; 19 | — |
| SECONDARY Number of Neonates With Suspected Neonatal Sepsis |
14; 16 | — |
| SECONDARY Number of Neonates With Neonatal Pneumonia |
1; 2 | — |
| SECONDARY Number of Neonates Experiencing Seizures / Encephalopathy |
0; 0 | — |
| SECONDARY Median Length of Neonatal Hospital Stay |
2; 2 | — |
| SECONDARY Number of Participants Experiencing Infant or Child Death |
10; 5 | — |
| SECONDARY Number of Children With Sensorineural Hearing Loss |
2; 7 | — |
| SECONDARY Number of Children Diagnosed With Chorioretinitis |
0; 1 | — |
| SECONDARY Mean Cognitive Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) |
96.2; 97.1 | — |
| SECONDARY Mean Motor Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) |
98.7; 101.9 | — |
| SECONDARY Number of Infants or Children With the Composite Outcome |
20; 15 | 0.37 |
| SECONDARY Overall Child Status at 24 Months of Age |
10; 5; 6; 7; 21; 19 | 0.26 |
| SECONDARY Failure to Thrive at 24 Months |
20; 21 | 0.84 |
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.
Eligibility Criteria
Inclusion Criteria
- 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.
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 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
Data sourced from ClinicalTrials.gov (NCT01376778). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.