A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
Ключови думи
Резюме
Описание
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.
Дати
| Последна проверка: | 01/31/2020 |
| Първо изпратено: | 06/14/2011 |
| Очаквано записване подадено: | 06/15/2011 |
| Първо публикувано: | 06/19/2011 |
| Изпратена последна актуализация: | 02/25/2020 |
| Последна актуализация публикувана: | 02/26/2020 |
| Действителна начална дата на проучването: | 03/31/2012 |
| Приблизителна дата на първично завършване: | 11/30/2018 |
| Очаквана дата на завършване на проучването: | 07/31/2021 |
Състояние или заболяване
Интервенция / лечение
Drug: CMV hyperimmune globulin - Cytogam®
Other: Placebo
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Active Comparator: CMV hyperimmune globulin - Cytogam® Infusion of Cytogam®, Cytomegalovirus Immune Globulin Intravenous (Human) (CMV-IGIV) | Drug: CMV hyperimmune globulin - Cytogam® 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 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. |
Критерии за допустимост
| Полове, допустими за проучване | Female |
| Приема здрави доброволци | Да |
| Критерии | 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 |
Резултат
Първични изходни мерки
1. Composite Outcome [3 weeks of life]
Вторични изходни мерки
1. Gestational hypertension [42 weeks of pregnancy]
2. Preeclampsia [42 weeks of pregnancy]
3. Placental abruption [42 weeks of pregnancy]
4. Gestational age at delivery [42 weeks of pregnancy]
5. Adverse reactions and side effects [Up to 42 weeks of pregnancy]
6. Fetal and neonatal mortality [24 months]
7. Primary outcome excluding terminations [3 weeks of life]
8. Head circumference [3 days of life]
9. Birth weight [1 day of life]
10. Growth restriction [1 day of life]
11. Microcephaly [3 days of life]
12. Symptomatic CMV infection [3 weeks of life]
13. Intraventricular hemorrhage [1 day of life]
14. Ventriculomegaly [1 day of life]
15. Retinopathy of prematurity (ROP) [participants will be followed for the duration of hospital stay, an expected average of 4 weeks]
16. Respiratory distress syndrome [participants will be followed for the duration of hospital stay, an expected average of 4 weeks]
17. Chronic lung disease [28 days of life]
18. Necrotizing enterocolitis (NEC) [participants will be followed for the duration of hospital stay, an expected average of 4 weeks]
19. Hyperbilirubinemia [participants will be followed for the duration of hospital stay, an expected average of 4 weeks]
20. Neonatal infectious morbidity [participants will be followed for the duration of hospital stay, an expected average of 4 weeks]
21. Seizures / encephalopathy [participants will be followed for the duration of hospital stay, an expected average of 4 weeks]
22. Length of hospital stay [participants will be followed for the duration of hospital stay, an expected average of 4 weeks]
23. Infant or child death [2 years of age]
24. Sensorineural hearing loss [12 and 24 months corrected age]
25. Chorioretinitis [2 years of age]
26. Cognitive and Motor Scores from the Bayley Certified Scales of Infant Development III [12 and 24 months corrected age]
27. Infant/Child composite outcome [2 years of age]
