Does a Rescue Course of Betamethasone in Pregnant Women With PPROM Decrease Neonatal Morbidity?
Primary Purpose
PPROM, Respiratory Distress Syndrome in Premature Infants
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Betamethasone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for PPROM focused on measuring preterm premature rupture of membranes, complications of prematurity, neonatal morbidity, respiratory distress syndrome, antenatal corticosteroids, betamethasone
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
Sites / Locations
- University of Texas Medical Branch in GalvestonRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Betamethasone
Saline Placebo
Arm Description
Women admitted with PPROM who will receive a second course of two betamethasone 12mg intramuscular (IM) injections given 24 hours apart.
Women admitted with PPROM who will receive intramuscular saline placebo, given as two injections 24 hours apart.
Outcomes
Primary Outcome Measures
Length of stay in the neonatal intensive care unit (NICU)
expressed in days
Secondary Outcome Measures
Composite neonatal morbidity
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
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)
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)
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
confirmed by culture in the first 72 hours of life
Necrotizing enterocolitis (NEC) stage 2 or 3
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
defined as stillbirth or death before neonatal discharge
Full Information
NCT ID
NCT02939742
First Posted
September 23, 2016
Last Updated
September 1, 2023
Sponsor
The University of Texas Medical Branch, Galveston
1. Study Identification
Unique Protocol Identification Number
NCT02939742
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 2016 (undefined)
Primary Completion Date
November 1, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Medical Branch, Galveston
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PPROM, Respiratory Distress Syndrome in Premature Infants
Keywords
preterm premature rupture of membranes, complications of prematurity, neonatal morbidity, respiratory distress syndrome, antenatal corticosteroids, betamethasone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
98 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Betamethasone
Arm Type
Experimental
Arm Description
Women admitted with PPROM who will receive a second course of two betamethasone 12mg intramuscular (IM) injections given 24 hours apart.
Arm Title
Saline Placebo
Arm Type
Placebo Comparator
Arm Description
Women admitted with PPROM who will receive intramuscular saline placebo, given as two injections 24 hours apart.
Intervention Type
Drug
Intervention Name(s)
Betamethasone
Other Intervention Name(s)
Celestone
Intervention Description
Betamethasone 12mg IM given every 24 hours for two doses
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline placebo
Intervention Description
Sterile 0.9% normal saline solution given IM every 24 hours for two doses
Primary Outcome Measure Information:
Title
Length of stay in the neonatal intensive care unit (NICU)
Description
expressed in days
Time Frame
daily from birth of infant up to one year
Secondary Outcome Measure Information:
Title
Composite neonatal morbidity
Description
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)
Time Frame
assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
Title
Duration of oxygen and ventilatory support
Description
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
Time Frame
assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
Title
Development of Respiratory Distress Syndrome (RDS)
Description
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
Time Frame
assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
Title
Grade III or IV intraventricular hemorrhage (IVH)
Description
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.
Time Frame
assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
Title
Neonatal Sepsis
Description
confirmed by culture in the first 72 hours of life
Time Frame
daily up to 72 hours of life
Title
Necrotizing enterocolitis (NEC) stage 2 or 3
Description
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.
Time Frame
assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
Title
Perinatal death
Description
defined as stillbirth or death before neonatal discharge
Time Frame
assessed daily up to 120 days after birth or discharge from hospital, whichever occurs first
Other Pre-specified Outcome Measures:
Title
Labor latency
Description
time from diagnosis of PPROM from admission until delivery of neonate or until completion of the study
Time Frame
time from admission to delivery up to one year, or through study completion
Title
Infectious morbidities
Description
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.
Time Frame
time from admission until maternal discharge from the hospital and up until 6 weeks postpartum, or through study completion
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Benjamin Bush, MD
Phone
(409)772-1571
Email
babush@utmb.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sara O Jacobs, MD
Phone
409-772-1571
Email
sojacobs@utmb.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Bush, MD
Organizational Affiliation
University of Texas Medical Branch in Galveston
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Medical Branch in Galveston
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Bush, MD
Phone
409-772-1571
Email
babush@utmb.edu
First Name & Middle Initial & Last Name & Degree
Ester Godbold, RN
Phone
409-772-0991
Email
esgodbol@utmb.edu
First Name & Middle Initial & Last Name & Degree
Benjamin Bush, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
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25422655
Citation
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Results Reference
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9932550
Citation
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Citation
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Citation
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Results Reference
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Citation
Mazumder P, Dutta S, Kaur J, Narang A. Single versus multiple courses of antenatal betamethasone and neonatal outcome: a randomized controlled trial. Indian Pediatr. 2008 Aug;45(8):661-7.
Results Reference
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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.
Results Reference
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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.
Results Reference
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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.
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Citation
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Results Reference
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Does a Rescue Course of Betamethasone in Pregnant Women With PPROM Decrease Neonatal Morbidity?
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