PPROM, Respiratory Distress Syndrome in Premature Infants
Conditions
Keywords
preterm premature rupture of membranes, complications of prematurity, neonatal morbidity, respiratory distress syndrome, antenatal corticosteroids, betamethasone
Brief summary
The purpose of this study is to determine if a repeat course of betamethasone given to pregnant women with preterm premature rupture of membranes (PPROM) will decrease the infant's length of stay in the neonatal intensive care unit (NICU) and the overall neonatal morbidity associated with this condition.
Detailed description
While the fetal benefits of a repeat course of antenatal corticosteroids have been demonstrated in several randomized controlled studies, to the investigators' knowledge they have not been adequately demonstrated in women with PPROM. Given the potential benefit of a repeat course of antenatal corticosteroids in women with PPROM on decreasing neonatal morbidity and the reassuring data from various cohorts on its safety, the investigators sought to propose a randomized controlled trial (RCT) with the hypothesis that a repeat course of antenatal corticosteroids in women with PPROM decreases neonatal morbidity. Objectives 1. To evaluate the impact of maternal treatment with a second course of betamethasone on infant length of stay in the NICU. 2. To evaluate the impact of maternal treatment with a second course of betamethasone on the duration of neonatal need for oxygen supplementation. 3. To evaluate the impact of maternal treatment with a second course of betamethasone on neonatal morbidity overall. Hypotheses The investigators hypothesize that treatment of women with PPROM between 24 and 34 weeks of gestation with a repeat course of antenatal corticosteroids decreases infant length of stay in the NICU and neonatal morbidity. Aim To describe and compare the neonatal outcomes of PPROM infants exposed to a repeat course of antenatal corticosteroids compared to infants in the same antenatal conditions who are exposed to only one betamethasone course. Subject Safety and Data Monitoring This study does not place subjects at risk of their safety. This medication is well studied and known to be safe in pregnancy. Data monitoring will be performed and viewed by study personnel only. The data will be de-identified and a study number will be assigned to each patient. The patient's identity will be secured on a UTMB encrypted laptop device and a hard copy stored in the locked file cabinet in the locked office of the principal investigator. Procedures to Maintain Confidentiality: Data will be viewed by study personnel only. The data will then be de-identified and a study number will be assigned to each patient. The patient's identity will then be secured on a UTMB encrypted laptop device and a hard copy stored in the locked file cabinet in the locked office of the principal investigator. Potential Benefits The potential benefits to subjects participating in the study include possible decreased neonatal morbidity and length of stay in the NICU. Biostatistics Using data from the University of Texas Medical Branch (UTMB) on women with PPROM between 24 and 34 weeks, who fit the inclusion criteria, and who received the standard one course of betamethasone, the average length of stay in the NICU was 59.3 ± 36.3 days. The gestational age at delivery in this cohort was 26.5 ± 3.2 weeks. Assuming that a second course of betamethasone reduces the length of stay needed in the NICU by 35%, and for a power of 80% and alpha 0.05, it is anticipated that enrollment of 49 women in each group will be needed, or 98 women total. At UTMB, there are approximately 400 women per year hospitalized with PPROM. Assuming 50% of eligible women consent, the investigators estimate to finish recruitment for this study in 1-2 years. Sample Size and Assumptions 1. Frequency of primary outcome in control group (single course of betamethasone): is 59.3 days. The investigators assume a 35% reduction in length of NICU stay using two courses of betamethasone. 2. α = 0.05, two sided 3. β = 0.2 4. Effect size: 35% reduction in primary outcome
Interventions
DRUGBetamethasone
Betamethasone 12mg IM given every 24 hours for two doses
DRUGPlacebo
Sterile 0.9% normal saline solution given IM every 24 hours for two doses
Sponsors
The University of Texas Medical Branch, Galveston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Maternal age ≥ 18 years * Preterm premature rupture of membranes, demonstrated clinically by speculum exam * Cervical dilation visually ≤ 5cm on sterile speculum exam * Planned delivery at John Sealy Hospital (JSH) * Gestational age of membrane rupture and initiation of first course of antenatal corticosteroids between 23 5/7 - 32 5/7 weeks * Planned pregnancy continuation with no indication for delivery for at least 7 days
Exclusion criteria
* Maternal age \> 50 years * Gestational age \< 23 5/7 weeks or \> 32 5/7 weeks * Known major congenital abnormalities, aneuploidy, or genetic syndrome * Intrauterine fetal demise * Any indication for expedited delivery * Maternal chorioamnionitis * Known allergy or adverse reaction to corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Days in the Neonatal Intensive Care Unit (NICU) | daily from birth of infant up to one year or discharge from the NICU, whichever occurred first | Mean number of days participants remained admitted to the Neonatal Intensive Care Unit (NICU) during hospitalization following birth. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Composite Neonatal Morbidity | assessed daily up to 120 days after birth or discharge from hospital, whichever occured first | defined as ≥ 1 of the following: RDS (oxygen requirement, clinical diagnosis, and consistent chest radiograph), bronchopulmonary dysplasia (requirement for oxygen support at 30 days of life), severe IVH (grades III or IV), periventricular leukomalacia, blood culture-proven sepsis, necrotizing enterocolitis, or perinatal death (stillbirth or death before neonatal hospital discharge) |
| Average Number of Days Requiring Supplemental Oxygen or Ventilatory Support | daily from birth until discharge from the NICU or up to 1 year of age, whichever occurred first. | Amount of time, expressed in days from birth, that the infant required supplemental oxygen of any form, including nasal cannula, positive airway pressure, or ventilatory support. Reported as the mean number of days participants required supplemental oxygen therapy or ventilatory support. |
| Number of Participants Who Developed Respiratory Distress Syndrome (RDS) | assessed daily up to 120 days after birth or discharge from hospital, whichever occurred first | Will be quantified as either present or absent. RDS defined as: compatible symptoms with radiographic evidence of hyaline membrane disease or respiratory insufficiency of prematurity requiring ventilatory support for ≥ 24 hrs |
| Grade III or IV Intraventricular Hemorrhage (IVH) | assessed daily up to 120 days after birth or discharge from hospital, whichever occurred first | Will be quantified as either present or absent. Grade III IVH defined as ventricles enlarged by accumulating blood. Grade IV IVH defined as bleeding extending into brain matter around the ventricles. |
| Number of Participants With Neonatal Sepsis | daily up to 72 hours of life | confirmed by culture in the first 72 hours of life |
| Number of Participants With Necrotizing Enterocolitis (NEC) Stage 2 or 3 | assessed daily up to 120 days after birth or discharge from hospital, whichever occurred first | Will be quantified as either present or absent. Stage 2 NEC will be defined as mild to moderate systemic illness, absent bowel sounds, abdominal tenderness, pneumatosis intestinalis or portal venous gas, metabolic acidosis, decreased platelets. Stage 3 NEC will be defined as severely ill, marked distention, signs of peritonitis, hypotension, metabolic \& respiratory acidosis, disseminated intravascular coagulopathy, pneumoperitoneum if bowel perforation present. |
| Number of Perinatal Death(s) | assessed daily up to 120 days after birth or discharge from hospital, whichever occurred first | defined as stillbirth or death before neonatal discharge |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBenjamin Bush, MD
University of Texas Medical Branch in Galveston
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 17 | 1 / 16 |
| other Total, other adverse events | 0 / 17 | 0 / 16 |
| serious Total, serious adverse events | 0 / 17 | 0 / 16 |
Outcome results
None listed