DETERMINE: Detemir vs NPH

Официальное название

A Phase 2 Open Label Randomized Controlled Trial Determir Vs Neutral Protamine Hagedorn (NPH) In Pregnant Women: DETERMINE Study

Обзор

The purpose of the study is to compare rates of neonatal hypoglycemia with maternal NPH vs determir use.

Подробное описание

Insulin detemir has been used and is FDA approved for type 1 diabetes in pregnancy women and its safety has been well established. At this point, the only long or intermediate acting medication that is approved for type 2 diabetes or gestational diabetes is insulin NPH. The most serious side effect of insulin detemir is hypoglycemia but the rates of hypoglycemia are lower when comparted to NPH both during pregnancy and outside of pregnancy. Diabetes mellitus (DM) is the most common diagnosis in pregnancy and its incidence is continuing to increase. Recent epidemiologic reports place the risk of pre-gestational diabetes at 1-2% and gestational diabetes (GDM) at 12.5%. Risk factors for type 2 diabetes (T2DM) and GDM include obesity, hypertension, family history of diabetes, polycystic ovarian syndrome, or excessive weight gain in pregnancy. Suboptimal control of DM in pregnancy confers significant morbidity on both the mother and fetus, including increased risk of preeclampsia, preterm delivery, perineal lacerations, cesarean delivery, neonatal hypoglycemia, and NICU admissions.

Вмешательства

• Препарат Insulin Detemir
  Patients are to receive insulin detemir
• Препарат Insulin NPH
  Patients are to receive insulin NPH

Первичные конечные точки

• Neonatal Hypoglycemia [Срок оценки: Within the first 24 hours of life]
• Prolonged neonatal hypoglycemia [Срок оценки: Neonatal hypoglycemia after the 1st 24 hours of life but before discharge]

Вторичные конечные точки (12)

• Neonatal Gastrin Level [Срок оценки: At birth]
• Neonatal C-Peptide Level [Срок оценки: At birth]
• Neonatal insulin level [Срок оценки: At birth]
• Neonatal leptin level [Срок оценки: At birth]
• Rates of pregnancy induced hypertension [Срок оценки: 1 year]
• Mode of delivery [Срок оценки: At delivery]
• Gestational Age at delivery [Срок оценки: At delivery]
• Maternal glycemic control [Срок оценки: 1 year]
• Total daily insulin [Срок оценки: 1 year]
• Fetal anomolies [Срок оценки: At birth]
• Macrosomia [Срок оценки: At birth]
• Polyhydramnios [Срок оценки: At birth]

Критерии участия

Критерии включения

• Inclusion criteria will include pregnant women with pre-existing T2DM and GDM who requiring insulin to manage their blood sugars in pregnancy.

Критерии исключения

• Multiple Gestation
• Type 1 Diabetes mellatus
• Age < 18
• Known or suspected hypersensitivity to NPH or insulin detemir
• Known fetal major malformations
• Chronic renal or hepatic insufficiency
• Known to be HIV, Hepatitis B, or Hepatitis C positive
• Indication for planned premature delivery (placenta accrete, or prior classical cesarean delivery)
• Insulin dependent before conception

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of California, Los Angeles — Los Angeles

Публикации

• Coton SJ, Nazareth I, Petersen I. A cohort study of trends in the prevalence of pregestational diabetes in pregnancy recorded in UK general practice between 1995 and 2012. BMJ Open. 2016 Jan 25;6(1):e009494. doi: 10.1136/bmjopen-2015-009494. PMID 26810997
• Melchior H, Kurch-Bek D, Mund M. The Prevalence of Gestational Diabetes. Dtsch Arztebl Int. 2017 Jul 16;114(24):412-418. doi: 10.3238/arztebl.2017.0412. PMID 28669379
• Mathiesen ER, Hod M, Ivanisevic M, Duran Garcia S, Brondsted L, Jovanovic L, Damm P, McCance DR; Detemir in Pregnancy Study Group. Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes. Diabetes Care. 2012 Oct;35(10):2012-7. doi: 10.2337/dc11-2264. Epub 2012 Jul 30. PMID 22851598
• Hirsch IB, Juneja R, Beals JM, Antalis CJ, Wright EE. The Evolution of Insulin and How it Informs Therapy and Treatment Choices. Endocr Rev. 2020 Oct 1;41(5):733-55. doi: 10.1210/endrev/bnaa015. PMID 32396624
• Herrera KM, Rosenn BM, Foroutan J, Bimson BE, Al Ibraheemi Z, Moshier EL, Brustman LE. Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes. Am J Obstet Gynecol. 2015 Sep;213(3):426.e1-7. doi: 10.1016/j.ajog.2015.06.010. Epub 2015 Jun 9. PMID 26070699
• Dalgic N, Ergenekon E, Soysal S, Koc E, Atalay Y, Gucuyener K. Transient neonatal hypoglycemia--long-term effects on neurodevelopmental outcome. J Pediatr Endocrinol Metab. 2002 Mar;15(3):319-24. doi: 10.1515/jpem.2002.15.3.319. PMID 11924935
• O'Neill SM, Kenny LC, Khashan AS, West HM, Smyth RM, Kearney PM. Different insulin types and regimens for pregnant women with pre-existing diabetes. Cochrane Database Syst Rev. 2017 Feb 3;2(2):CD011880. doi: 10.1002/14651858.CD011880.pub2. PMID 28156005
• Kadakia R, Talbot O, Kuang A, Bain JR, Muehlbauer MJ, Stevens RD, Ilkayeva OR, Lowe LP, Metzger BE, Newgard CB, Scholtens DM, Lowe WL; HAPO Study Cooperative Research Group. Cord Blood Metabolomics: Association With Newborn Anthropometrics and C-Peptide Across Ancestries. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4459-4472. doi: 10.1210/jc.2019-00238. PMID 31498869

Идентификаторы

NCT: NCT05124457 · DETERMINE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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