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

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

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

Study Overview

• Status: Recruiting
• Conditions: Twin Pregnancy, Antepartum Condition or Complication
• Intervention / Treatment: Drug: Betamethason Sodium Phosphate; Drug: Normal saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 808
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Seung Mi Lee; Phone Number: +82-2-2072-4857; Email: smleemd@hanmail.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ACS (Group 1); Intramuscular injection of betamethason sodium phosphate 12mg (3ml) twice 24hours apart	Drug: Betamethason Sodium Phosphate; 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.; Other Names: ACS
Placebo Comparator: Placebo (Group 2); Intramuscular injection of normal saline 3ml twice 24hours apart	Drug: Normal saline; Intramuscular injection of normal saline 3ml twice 24hours apart; Other Names: NS

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Necrotizing enterocolitis (NEC)	meconium plug syndrome or confirmed NEC by pathohistology or operation finding	28 days after birth
Birth weight	neonatal body weight	at birth
1 minute, 5minute Apgar score	evaluation(scoring) of neonatal appearance, pulse, grimace, activity, respiration 1 minute and 5minute after birth	at birth
Hypoglycemia	Glucose < 40 mg%	28 days after birth
Hyperbilirubinemia	Peak total bilirubin of at least 15 mg% or the use of phototherapy	28 days after birth
Feeding difficulty	Inability to take all feeds (po), i.e. requiring gavage feeds or IV supplementation. In addition, time to first feed (po) will be recorded	28 days after birth
Neonatal infectious morbidity	Sepsis, Suspected sepsis and Pneumonia	28 days after birth
Seizures / encephalopathy	Witnessed seizure	28 days after birth
Hospital day of NICU admission	Includes need for NICU or intermediate care admission and length of stay if admitted	28 days after birth

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Publications and helpful links

General Publications

• McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020 Dec 25;12(12):CD004454. doi: 10.1002/14651858.CD004454.pub4.
• Hong S, Lee SM, Kwak DW, Lee J, Kim SY, Oh JW, Oh S, Park CW, Park JS, Chung JH, Jun JK. Effects of antenatal corticosteroids in twin neonates with late preterm birth (ACTWIN [Antenatal Corticosteroids in TWIN late preterm neonates] trial): study protocol for a randomized controlled trial. BMC Pregnancy Childbirth. 2019 Apr 3;19(1):114. doi: 10.1186/s12884-019-2235-5.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2018
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 23, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Antenatal corticosteroid; Twin pregnancies; Respiratory morbidity
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Betamethasone; Betamethasone Valerate; Betamethasone-17,21-dipropionate; Betamethasone benzoate; Betamethasone sodium phosphate
• Other Study ID Numbers: Twin_RCT_2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No