Clinical trial NCT02939742: Does a Rescue Course of Betamethasone in Pregnant Women With PPROM Decrease Neonatal Morbidity?
Official title: Does a Repeat Course of Antenatal Corticosteroids in Pregnant Women With Preterm Premature Rupture of Membranes Decrease Neonatal Morbidity?
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: PPROM
Respiratory Distress Syndrome in Premature Infants
Keywords: preterm premature rupture of membranes
complications of prematurity
neonatal morbidity
respiratory distress syndrome
antenatal corticosteroids
betamethasone
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
First posted: 2016-10-20
Enrollment: 33
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Length of stay in the neonatal intensive care unit (NICU)
timeFrame: daily from birth of infant up to one year
Secondary outcomes:
measure: Composite neonatal morbidity
timeFrame: assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
measure: Duration of oxygen and ventilatory support
timeFrame: assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
measure: Development of Respiratory Distress Syndrome (RDS)
timeFrame: assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
measure: Grade III or IV intraventricular hemorrhage (IVH)
timeFrame: assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
measure: Neonatal Sepsis
timeFrame: daily up to 72 hours of life
measure: Necrotizing enterocolitis (NEC) stage 2 or 3
timeFrame: assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
measure: Perinatal death
timeFrame: assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
Other outcomes:
measure: Labor latency
timeFrame: time from admission to delivery up to one year, or through study completion
measure: Infectious morbidities
timeFrame: time from admission until maternal discharge from the hospital and up until 6 weeks postpartum, or through study completion
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch in Galveston
state: Texas
Study officials:
affiliation: University of Texas Medical Branch in Galveston
name: Benjamin Bush, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Atarod Z, Taghipour M, Roohanizadeh H, Fadavi S, Taghavipour M. Effects of single course and multicourse betamethasone prior to birth in the prognosis of the preterm neonates: A randomized, double-blind placebo-control clinical trial study. J Res Med Sci. 2014 Aug;19(8):715-9.
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citation: National Institutes of Health Consensus Development Panel. Antenatal corticosteroids revisited: repeat courses - National Institutes of Health Consensus Development Conference Statement, August 17-18, 2000. Obstet Gynecol. 2001 Jul;98(1):144-50. doi: 10.1016/s0029-7844(01)01410-7.
citation: Practice bulletins No. 139: premature rupture of membranes. Obstet Gynecol. 2013 Oct;122(4):918-930. doi: 10.1097/01.AOG.0000435415.21944.8f.
citation: Wijnberger LD, Mostert JM, van Dam KI, Mol BW, Brouwers H, Visser GH. Comparison of single and repeated antenatal corticosteroid therapy to prevent neonatal death and morbidity in the preterm infant. Early Hum Dev. 2002 Apr;67(1-2):29-36. doi: 10.1016/s0378-3782(01)00248-1.
citation: Yang SH, Choi SJ, Roh CR, Kim JH. Multiple courses of antenatal corticosteroid therapy in patients with preterm premature rupture of membranes. J Perinat Med. 2004;32(1):42-8. doi: 10.1515/JPM.2004.007.