Does a Rescue Course of Betamethasone in Pregnant Women With PPROM Decrease Neonatal Morbidity?

Sponsor

The University of Texas Medical Branch, Galveston (Other)

Overall Status

Recruiting

CT.gov ID

NCT02939742

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
PPROM Respiratory Distress Syndrome in Premature Infants	Drug: Betamethasone Drug: Placebo	Phase 2/Phase 3

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

To evaluate the impact of maternal treatment with a second course of betamethasone on infant length of stay in the NICU.
To evaluate the impact of maternal treatment with a second course of betamethasone on the duration of neonatal need for oxygen supplementation.
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

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.
α = 0.05, two sided
β = 0.2
Effect size: 35% reduction in primary outcome

Study Design

Study Type:

Interventional

Anticipated Enrollment :

98 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Does a Repeat Course of Antenatal Corticosteroids in Pregnant Women With Preterm Premature Rupture of Membranes Decrease Neonatal Morbidity?

Study Start Date :

Nov 1, 2016

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Betamethasone Women admitted with PPROM who will receive a second course of two betamethasone 12mg intramuscular (IM) injections given 24 hours apart.	Drug: Betamethasone Betamethasone 12mg IM given every 24 hours for two doses Other Names: Celestone
Placebo Comparator: Saline Placebo Women admitted with PPROM who will receive intramuscular saline placebo, given as two injections 24 hours apart.	Drug: Placebo Sterile 0.9% normal saline solution given IM every 24 hours for two doses Other Names: Saline placebo

Arm

Intervention/Treatment

Experimental: Betamethasone

Women admitted with PPROM who will receive a second course of two betamethasone 12mg intramuscular (IM) injections given 24 hours apart.

Drug: Betamethasone

Betamethasone 12mg IM given every 24 hours for two doses

Other Names:

Celestone

Placebo Comparator: Saline Placebo

Women admitted with PPROM who will receive intramuscular saline placebo, given as two injections 24 hours apart.

Drug: Placebo

Sterile 0.9% normal saline solution given IM every 24 hours for two doses

Other Names:

Saline placebo

Outcome Measures

Primary Outcome Measures

Length of stay in the neonatal intensive care unit (NICU) [daily from birth of infant up to one year]
expressed in days

Secondary Outcome Measures

Composite neonatal morbidity [assessed daily up to 120 days after birth or discharge from hospital, whichever occurs 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)
Duration of oxygen and ventilatory support [assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first]
Amount of time in days from birth that the infant requires supplemental oxygen of any form, including nasal cannula, positive airway pressure, or ventilatory support
Development of Respiratory Distress Syndrome (RDS) [assessed daily up to 120 days after birth or discharge from hospital, whichever occurs 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 occurs 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.
Neonatal Sepsis [daily up to 72 hours of life]
confirmed by culture in the first 72 hours of life
Necrotizing enterocolitis (NEC) stage 2 or 3 [assessed daily up to 120 days after birth or discharge from hospital, whichever occurs 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.
Perinatal death [assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first]
defined as stillbirth or death before neonatal discharge

Other Outcome Measures

Labor latency [time from admission to delivery up to one year, or through study completion]
time from diagnosis of PPROM from admission until delivery of neonate or until completion of the study
Infectious morbidities [time from admission until maternal discharge from the hospital and up until 6 weeks postpartum, or through study completion]
Chorioamnionitis will be defined as at least one temperature elevation above 38°C combined with at least two of the following signs: maternal or fetal tachycardia, uterine tenderness, foul smelling vaginal discharge, white blood count > 18,000. Postpartum endometritis will be defined as postpartum temperature elevation above 38°C without other localizing sources of infection and with either uterine tenderness or foul-smelling lochia.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts 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