Effects of ACS in Twin With LPB: Study Protocol for a RCT

Study Overview
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Brief Summary
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This study will be the first study that evaluates the effectiveness of antenatal corticosteroid (ACS) in late preterm twin neonates.

Detailed Description
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Antenatal corticosteroid (ACS) has been proven to prevent adverse outcomes including respiratory morbidities in preterm neonates before 34 weeks of gestations. Recently, it has been suggested that ACS may be also effective for reduction of respiratory complications in singleton late preterm pregnancies. On the contrary, there is a paucity of information regarding the effectiveness of ACS in twin neonates with late preterm birth, and nowadays guidelines are recommending the use of ACS in twin pregnancies based on the evidences in singleton pregnancies. However, the effect of ACS in twin needs to be determined, because the rate of neonatal morbidities in twin preterm neonates seems to be different from that in singleton neonates. This study aims to determine the effectiveness of ACS in late preterm twin neonates.

Official Title
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Effects of Antenatal Corticosteroid in Twin Neonates With Late Preterm Birth: Study Protocol for a Randomized Controlled Trial

Conditions
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Twin Pregnancy, Antepartum Condition or Complication

Intervention / Treatment
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* Drug: Betamethason Sodium Phosphate
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) Age over 18 years (2) Twin pregnant women at 34weeks 0days to 36weeks 5days of gestation (3) At risk for preterm birth such as preterm labor, preterm prematrue rupture of membrane or maternal-fetal indications that need preterm delivery. Preterm labor is defined as regular uterine contractions with or without the following symptoms; pelvic pressure, backache, increased vaginal discharge, menstrual-like cramps, bleeding/show, cervical changes (4) Availability of written informed consent. Exclusion Criteria: (1) Gestational age before 34weeks 0days or after 36weeks 6days (2) Lethal major fetal anomaly, fetal distress or fetal death in utero (3) Expected to deliver within 12 hours; for example, advanced cervical dilatation (>8cm) in preterm labor or active phase labor (cervical dilatation>4cm) in preterm premature rupture of membranes (4) History of a previous administration of ACS before 34weeks of gestation for fetal lung maturation (5) Administration of systemic steroid for medical indications (6)Diagnosis of clinical chorioamnionitis Fever >37.8 and the presence of two more following conditions: uterine tenderness, foul-odored vaginal discharge, maternal leukocytosis(>1500), maternal tachycardia(>100) or fetal tachycardia(>160)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In this multi-center, double-blind, randomized, placebo-controlled trial, women who are at risk for late preterm birth (34+0wks-36+5wks) will be enrolled and randomly assigned to two groups receiving betamethasone(ACS) or placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACS (Group 1)<br>Intramuscular injection of betamethason sodium phosphate 12mg (3ml) twice 24hours apart | Drug: Betamethason Sodium Phosphate<br>* The antecorticosteroid that will be administered to Group 1 is betamethasone, produced by Dawon Parm(Korea). It contains betamethason sodium phosphate 5.2mg(Betamethasone 4.0mg) in 1 ample(1mL). Each drug is carried in a syringe by pharmacist who does not participate in study after the patient was enrolled in the study and administered to the patient twice 24hours apart.<br>* Other names: ACS;|
| Placebo Comparator: Placebo (Group 2)<br>Intramuscular injection of normal saline 3ml twice 24hours apart | Drug: Normal saline<br>* Intramuscular injection of normal saline 3ml twice 24hours apart<br>* Other names: NS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of respiratory morbidity | NICU admission, Continuous positive airway pressure, High flow nasal cannula for ≥12 continuous hours, Fraction of inspired oxygen of ≥ 0.3, Mechanical ventilation use, ECMO use and Stillbirth or neonatal death within 72hours after death | 72 hours after birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal complication | Chorioamnionitis and Postpartum endometritis | 72 hours after birth | 
| Respiratory distress syndrome | Presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with a requirement for supplemental oxygen with a fraction of inspired oxygen of more than 0.21 and a chest radiograph showing hypoaeration and reticulogranular infiltrates | 72 hours after birth | 
| Transient tachypnea of the newborn, apnea | Tachypnea occurred in the absence of chest radiography or with a radiograph that was normal or showed signs of increased perihilar interstitial markings and resolved within 72 hours | 72 hours after birth | 
| Need for resuscitation at birth | any intervention in the first 30 minutes other than blow-by oxygen | at birth | 
| Surfactant use | Surfactant use | 28 days after birth | 
| Bronchopulmonary dysplasia;BPD | Requirement for supplemental oxygen with a fraction of inspired oxygen of more than 0.21 for the first 28 days of life | 28 days after birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antenatal corticosteroid, Twin pregnancies, Respiratory morbidity, Randomized controlled trial