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

The University of Texas System (UT)

Status and phase: Terminated; Phase 3; Phase 2

Conditions: PPROM; Respiratory Distress Syndrome in Premature Infants

Treatments: Drug: Placebo; Drug: Betamethasone

Study type: Interventional

Funder types: Other

Identifiers

NCT02939742

15-0280

Details and patient eligibility

About

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.

Full 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

Enrollment: 33 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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33 participants in 2 patient groups, including a placebo group

Betamethasone

Experimental group

Description:

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

Treatment:

Drug: Betamethasone

Saline Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo