Euglycemia After Antenatal Late Preterm Steroids, the E-ALPS Study

NCT03076775 | Completed Results DMC

• 2 other identifiers: 18-19701R03HD096188-01
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 2

Brief Summary

Annually in the U.S 300,000 neonates are born late preterm, defined as 34 weeks 0 days - 36 weeks 6 days. The Antenatal Late Preterm Steroids (ALPS) Trial demonstrated that maternal treatment with betamethasone in the late preterm period significantly reduces neonatal respiratory complications, but also increases neonatal hypoglycemia, compared to placebo. This research study will attempt to answer the following primary question: Does a management protocol aimed at maintaining maternal euglycemia after ALPS decrease fetal hyperinsulinemia, compared to usual antepartum care?

Conditions

Pregnancy Preterm; Neonatal Hypoglycemia; Hyperglycemia Drug Induced

Keywords

Betamethasone; Late preterm; Steroids

Outcome Measures

Primary Outcomes (1)

• Umbilical Cord Blood C-peptide

  C-peptide level (ng/mL) as measure of fetal hyperinsulinemia

  At delivery

Secondary Outcomes (14)

• Umbilical Cord Blood Cortisol

  At delivery

• Umbilical Insulin-Like Growth Factor 1

  At delivery

• Umbilical Cord Blood Leptin

  At delivery

• Neonatal Hypoglycemia

  After birth, up to 48 hours of life

• Neonatal Hypoglycemia Treatment

  After birth, during hospital admission, assessed up to 28 days

Study Arms (2)

Intervention

EXPERIMENTAL

Women will undergo regular maternal blood glucose screening and treatment of hyperglycemia following BMZ administration to achieve maternal glycemic control until delivery or hospital discharge, for a maximum of 5 days.

Other: Maternal glycemic control

Usual Care

NO INTERVENTION

Routine antenatal care will be performed without any maternal blood glucose screening nor treatment as is usual care at each of the study sites.

Interventions

Maternal glycemic control OTHER

Maternal capillary blood glucose testing will be performed according to oral intake status: every 2 hours if not eating (NPO) or fasting and 1-hour postprandial if eating regular meals. Hyperglycemia, defined based on the American Diabetes Association and the American College of Obstetricians and Gynecologists recommendations as well as current practice at study sites, will be treated according to study guidelines based on oral intake status: insulin infusion if NPO and subcutaneous insulin if eating regular meals.

Intervention

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Recruiting pregnant females
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Singleton gestation with no known major fetal anomalies
• Gestational age at randomization between 34 weeks 0 days and 36 weeks 5 days
• Receiving antenatal betamethasone due to high probability of delivery in late preterm period

You may not qualify if:

• Pre-gestational or gestational diabetes mellitus
• Maternal contraindication to insulin
• Planned outpatient treatment with antenatal betamethasone
• Participation in clinical trial that could affect primary outcome or participation in this trial in a previous pregnancy

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (17)

• Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, Rouse DJ, McKenna DS, Clark EA, Thorp JM Jr, Chien EK, Peaceman AM, Gibbs RS, Swamy GK, Norton ME, Casey BM, Caritis SN, Tolosa JE, Sorokin Y, VanDorsten JP, Jain L; NICHD Maternal-Fetal Medicine Units Network. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. N Engl J Med. 2016 Apr 7;374(14):1311-20. doi: 10.1056/NEJMoa1516783. Epub 2016 Feb 4.

  PMID: 26842679 BACKGROUND

• Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Mathews TJ. Births: Final Data for 2015. Natl Vital Stat Rep. 2017 Jan;66(1):1.

  PMID: 28135188 BACKGROUND

• McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008 Jan;111(1):35-41. doi: 10.1097/01.AOG.0000297311.33046.73.

  PMID: 18165390 BACKGROUND

• Consortium on Safe Labor; Hibbard JU, Wilkins I, Sun L, Gregory K, Haberman S, Hoffman M, Kominiarek MA, Reddy U, Bailit J, Branch DW, Burkman R, Gonzalez Quintero VH, Hatjis CG, Landy H, Ramirez M, VanVeldhuisen P, Troendle J, Zhang J. Respiratory morbidity in late preterm births. JAMA. 2010 Jul 28;304(4):419-25. doi: 10.1001/jama.2010.1015.

  PMID: 20664042 BACKGROUND

• Gilbert WM, Nesbitt TS, Danielsen B. The cost of prematurity: quantification by gestational age and birth weight. Obstet Gynecol. 2003 Sep;102(3):488-92. doi: 10.1016/s0029-7844(03)00617-3.

  PMID: 12962929 BACKGROUND

• Jolley JA, Rajan PV, Petersen R, Fong A, Wing DA. Effect of antenatal betamethasone on blood glucose levels in women with and without diabetes. Diabetes Res Clin Pract. 2016 Aug;118:98-104. doi: 10.1016/j.diabres.2016.06.005. Epub 2016 Jun 17.

  PMID: 27351800 BACKGROUND

• Langen ES, Kuperstock JL, Sung JF, Taslimi M, Byrne J, El-Sayed YY. Maternal glucose response to betamethasone administration. Am J Perinatol. 2015 Feb;30(2):143-8. doi: 10.1055/s-0034-1376387. Epub 2014 Jun 10.

  PMID: 24915559 BACKGROUND

• Shelton SD, Boggess KA, Smith T, Herbert WN. Effect of betamethasone on maternal glucose. J Matern Fetal Neonatal Med. 2002 Sep;12(3):191-5. doi: 10.1080/jmf.12.3.191.195.

  PMID: 12530617 BACKGROUND

• Refuerzo JS, Garg A, Rech B, Ramin SM, Vidaeff A, Blackwell SC. Continuous glucose monitoring in diabetic women following antenatal corticosteroid therapy: a pilot study. Am J Perinatol. 2012 May;29(5):335-8. doi: 10.1055/s-0031-1295642. Epub 2011 Nov 17.

  PMID: 22094918 BACKGROUND

• Sifianou P, Thanou V, Karga H. Metabolic and hormonal effects of antenatal betamethasone after 35 weeks of gestation. J Pediatr Pharmacol Ther. 2015 Mar-Apr;20(2):138-43. doi: 10.5863/1551-6776-20.2.138.

  PMID: 25964731 BACKGROUND

• Obenshain SS, Adam PA, King KC, Teramo K, Raivio KO, Raiha N, Schwartz R. Human fetal insulin response to sustained maternal hyperglycemia. N Engl J Med. 1970 Sep 10;283(11):566-70. doi: 10.1056/NEJM197009102831104. No abstract available.

  PMID: 5450610 BACKGROUND

• Kuhl C, Andersen GE, Hertel J, Molsted-Pedersen L. Metabolic events in infants of diabetic mothers during first 24 hours after birth. I. Changes in plasma glucose, insulin and glucagon. Acta Paediatr Scand. 1982 Jan;71(1):19-25. doi: 10.1111/j.1651-2227.1982.tb09366.x.

  PMID: 6753468 BACKGROUND

• American College of Obstetricians and Gynecologists' Committee on Obstetric Practice; Society for Maternal- Fetal Medicine. Committee Opinion No.677: Antenatal Corticosteroid Therapy for Fetal Maturation. Obstet Gynecol. 2016 Oct;128(4):e187-94. doi: 10.1097/AOG.0000000000001715.

  PMID: 27661658 BACKGROUND

• Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016 Aug;215(2):B13-5. doi: 10.1016/j.ajog.2016.03.013. Epub 2016 Mar 15. No abstract available.

  PMID: 26992737 BACKGROUND

• ACOG Committee on Practice Bulletins. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Number 60, March 2005. Pregestational diabetes mellitus. Obstet Gynecol. 2005 Mar;105(3):675-85. doi: 10.1097/00006250-200503000-00049. No abstract available.

  PMID: 15738045 BACKGROUND

• American Diabetes Association. Standards of medical care in diabetes - 2016. Diabetes Care. 2016; 39(suppl1):S1-S106.

  BACKGROUND

• Battarbee AN, Ye Y, Szychowski JM, Casey BM, Tita AT, Boggess KA. Euglycemia after antenatal late preterm steroids: a multicenter, randomized controlled trial. Am J Obstet Gynecol MFM. 2022 Jul;4(4):100625. doi: 10.1016/j.ajogmf.2022.100625. Epub 2022 Mar 26.

  PMID: 35346889 DERIVED

Results Point of Contact

• Title: Ashley Battarbee, MD, MSCR
• Organization: University of North Carolina at Chapel Hill

anbattarbee@uabmc.edu

205-975-2361

Study Officials

• Ashley N Battarbee, MD, MSCR

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Kim Boggess, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 10, 2017
• Study Start: June 8, 2017
• Primary Completion: February 18, 2021
• Study Completion: November 19, 2021
• Last Updated: January 26, 2022
• Results First Posted: January 26, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)