Low Dose Antenatal Corticosteroids for Late Preterm Delivery (LoDAC)

Low Dose Antenatal Corticosteroids for Late Preterm Delivery (LoDAC Study)

This is a study proposal for a clinical trial to evaluate the effectiveness of a reduced dose of antenatal betamethasone (a steroid medication) in preventing respiratory problems in late preterm infants (born between 34 and 36 weeks of gestation). The study will be conducted in medical centers in Israel and will involve women who are at high risk for delivering a late preterm infant. The participants will be randomly assigned to receive either a full dose (12 mg) or a quarter dose (3 mg) of betamethasone, administered 24 hours apart. The main outcome measure of the study will be the incidence of respiratory problems or neonatal death within 72 hours of delivery in the two groups. The study is designed to determine if the reduced dose of betamethasone is non-inferior (i.e., not significantly worse) than the full dose in preventing respiratory problems in late preterm infants.

Study Overview

• Status: Recruiting
• Conditions: Preterm Labor; Respiratory Morbidity
• Intervention / Treatment: Other: we will use reduced dose of acceptable corticosteroids treatment for preterm birth

Detailed Description

Antenatal corticosteroids (ACS) are a type of steroid medication that is administered to pregnant women at risk of preterm birth in order to reduce the risk of respiratory distress syndrome (RDS) and other complications in the newborn. ACS were first demonstrated to be effective in a controlled trial conducted in the 1970s by Liggins and Howie, who used a combination of betamethasone at a dose of 12 mg given in two doses 24 hours apart. Since then, numerous randomized controlled trials and meta-analyses have shown that ACS can significantly reduce neonatal death, RDS, intraventricular hemorrhage, necrotizing enterocolitis, and the need for respiratory support and neonatal intensive care unit admission in preterm infants. ACS are now recommended for use in virtually all pregnancies at risk of preterm delivery between 24 and 34 weeks of gestation. The use of ACS in late preterm pregnancies (between 34 and 37 weeks) has also been studied, with mixed results. The largest study to date, the ALPS trial, found that ACS reduced composite adverse outcomes and respiratory morbidity in late preterm infants, but did not significantly reduce the risk of RDS or mortality. The American Congress of Obstetricians and Gynecologists has recommended the use of ACS in late preterm pregnancies, but with caution due to the potential for adverse effects such as hypoglycemia. Long-term follow-up studies are needed to evaluate the potential long-term effects of ACS in late preterm infants. In this the participants will be randomly assigned to receive either a full dose (12 mg) or a quarter dose (3 mg) of betamethasone, administered 24 hours apart. The main outcome measure of the study will be the incidence of respiratory problems or neonatal death within 72 hours of delivery in the two groups. The study is designed to determine if the reduced dose of betamethasone is non-inferior (i.e., not significantly worse) than the full dose in preventing respiratory problems in late preterm infants.

• Study Type: Interventional
• Enrollment (Estimated): 1510
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ron Beloosesky, MD; Phone Number: 0509205759; Email: tomor2304@yahoo.com

Study Locations

• Israel
  • Afula, Israel
    • Recruiting
    • Emek Medical Center
    • Contact: Noa Zafran, MD
  • Ashkelon, Israel
    • Recruiting
    • Kaplan Medical Center
    • Contact: Edi Vaisbuch, MD
  • Be'er Sheva, Israel
    • Recruiting
    • Soroka Medical Center
    • Contact: Noa Aleluya, MD
  • Hadera, Israel
    • Recruiting
    • Hilel Yafee Medical Center
    • Contact: Rinat Gabbay, MD
  • Haifa, Israel
    • Recruiting
    • Bnai Zion Medical Center
    • Contact: Rami Sammour, MD
  • Haifa, Israel
    • Recruiting
    • Carmel Medical Center
    • Contact: Nir Kugelman, MD
  • Haifa, Israel
    • Recruiting
    • Rambam Health Care Cmpus
    • Principal Investigator: Ron Beloosesky, M.D
  • Jerusalem, Israel
    • Recruiting
    • Shaare Zedek Medical Center
    • Contact: Sorina Grisaru, MD
  • Jerusalem, Israel
    • Recruiting
    • Hadassah Ein Karem
    • Contact: Doron Cabiri
  • Jerusalem, Israel
    • Recruiting
    • Hadassah Har Hzofim
    • Contact: Lorin Levit Rosen, MD
  • Kfar Saba, Israel
    • Recruiting
    • Meir Medical Center
    • Contact: Or Elinor, MD
  • Nahariya, Israel
    • Recruiting
    • Galilee Medical Center
    • Contact: Maya Wolf, MD
  • Petach Tikva, Israel
    • Recruiting
    • Rabin Medical Center
    • Contact: Sivan Easton, MD
  • Ramat Gan, Israel
    • Recruiting
    • Sheba Medical Center
    • Contact: Yoav Yinon, MD
  • Tel Aviv, Israel
    • Recruiting
    • Sourasky Medical Center
    • Contact: Liran Hirsh
  • Zefat, Israel
    • Recruiting
    • ZIV Medical Center
    • Contact: Yael Sciaky-Tamir, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:- - Singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation at risk for / high probability of delivery in the late preterm period (34+0-36+5 weeks of gestation).

Criteria for determination of late preterm delivery risk:

1. Preterm uterine contractions with intact membranes, and at least 3 cm dilation or 75% cervical effacement
2. Spontaneous rupture of the membranes

3. Expected preterm delivery for any other indication via induction or cesarean between 24 hours to 7 days after the planned randomization, as determined by the obstetric provider.

   -

   Exclusion Criteria: They had already received a full course of betamethasone.

   • Expected delivery in less than 12 hours, irrespective of cause including: 1)ruptured membranes in the presence of more than 6 contractions per hour or cervical dilation of 3 centimeters or more unless oxytocin was withheld for at least 12 hours (although other induction agents were allowed), 2) chorioamnionitis, 3) cervical dilation of 8 cm or more, and 4) evidence of non-reassuring fetal status requiring immediate delivery.
   • Prior ACS treatment
   • Current known or suspected infection ( viral, bacterial or other)
   • Pre-gestational diabetes mellitus.
   • Any infection that required antibiotics or hospitalization in the month prior to study allocation - Poor understanding of the inform consent language

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: betamethasone 12 mg; 3 mg betamethasone sodium phosphate and 3 mg betamethasone acetate per milliliter. The first dose of study drug medication will be administered at randomization as 2 ml injection; the next dose of 2 ml will be administered 24 hours later	Other: we will use reduced dose of acceptable corticosteroids treatment for preterm birth; the two different group will differ in the doses of corticosteroids
Experimental: betamethasone 3 mg; 3 mg betamethasone sodium phosphate and 3 mg betamethasone acetate per milliliter. The first dose of study drug medication will be administered at randomization as 0.5 ml injection; the next dose of 0.5 ml will be administered 24 hours later	Other: we will use reduced dose of acceptable corticosteroids treatment for preterm birth; the two different group will differ in the doses of corticosteroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory morbidity	Use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for ≥2 continuous hr in the first 72 hours; Fraction of inspired oxygen of ≥0.30 for ≥4 continuous hr in the first 72 hours; Mechanical ventilation in the firdt 72 hours yes/no; extracorporeal membrane oxygenation (ECMO) yes/no; TTN: transient tachypnea of newborn yes/no	first 72 hours after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
other neonatal morbidities other neonatal morbidities	for all the parameters: yes or no Severe respiratory complications (a composite outcome of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least at least 24 continuous hours, ECMO or mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) Respiratory distress syndrome, Transient tachypnea of the newborn, Apnea, Bronchopulmonary dysplasia, Surfactant administration, Need for resuscitation at birth , Feeding difficulty, Hypothermia, , Necrotizing enterocolitis, Intraventricular hemorrhage Papile grade 3 or 4, Neonatal sepsis, Pneumonia, Pulmonary air leak, Death before discharge Newborns blood levels of glucose: mg/dl insulin and c-peptide : levels in serum	first 30 days after birth

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 31, 2022
• First Submitted That Met QC Criteria: January 16, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: corticosteroids; low dose; late prerterm
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Obstetric Labor, Premature
• Other Study ID Numbers: 00451890

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