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

NCT ID: NCT03076775

Last Updated: 2022-01-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-08

Study Completion Date

2021-11-19

Brief Summary

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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?

Detailed Description

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Euglycemia after Antenatal Late Preterm Steroids, the E-ALPS Study:

There is a fundamental gap in understanding the adverse metabolic effects of antenatal late preterm steroids (ALPS). In 2016, an important randomized clinical trial of 2827 late preterm pregnancies showed that antenatal betamethasone (BMZ) significantly reduced neonatal respiratory complications compared with placebo. However, those neonates exposed to BMZ were also more likely to have hypoglycemia at birth. This unexpected adverse outcome raised concern among both obstetricians and neonatologists and remains an important knowledge gap to be filled. The rationale for the proposed research is that steroid-induced maternal hyperglycemia leads to transient fetal hyperinsulinemia, which causes hypoglycemia in neonates that are delivered during this time-period. Thus, the fetal metabolic consequences and subsequent neonatal hypoglycemia observed after exposure to BMZ in utero can be prevented by achieving maternal euglycemia prior to delivery.

This protocol describes a randomized clinical trial to evaluate whether screening for and treatment of steroid-induced hyperglycemia in non-diabetic women treated with BMZ in the late preterm period can decrease the rate of fetal hyperinsulinemia, thus reducing neonatal hypoglycemia and improving short-term neonatal outcomes.

This study was formerly approved as Institutional Review Board #16-3200.

Conditions

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Pregnancy Preterm Neonatal Hypoglycemia Hyperglycemia Drug Induced

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Intervention

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.

Group Type EXPERIMENTAL

Maternal glycemic control

Intervention Type 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.

Usual Care

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Maternal glycemic control

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 Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ashley N Battarbee, MD, MSCR

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Kim Boggess, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 26842679 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 28135188 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18165390 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20664042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12962929 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27351800 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24915559 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12530617 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22094918 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25964731 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 5450610 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6753468 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27661658 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26992737 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15738045 (View on PubMed)

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

Reference Type 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.

Reference Type DERIVED
PMID: 35346889 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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1R03HD096188-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18-1970

Identifier Type: -

Identifier Source: org_study_id

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