Pregnancy Outcomes: Effects of Metformin Study (POEM Study) a long term randomized controlled parallel group study in gestational diabetes mellitus
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 500
- 试验地点
- 7
- 主要终点
- Phase A: GDM Outcome Score (= GOS), an ordinal variable (range 0-8) per pregnancy: (1) pregnancy related hypertension, including pre-eclampsia and eclampsia, (2) large for gestational age (LGA) at delivery (neonatal weight > 90th percentile), (3) premature delivery (< 37.0 weeks of gestation), (4) instrumental delivery, (5) caesarean delivery, (6) birth trauma, (7) neonatal hypoglycaemia (< 2.6 mmol/l), and (8) admission to the NICU.
研究概览
简要总结
The central aim is to investigate whether metformin from the start of the diagnosis GDM on top of standard of care may improve the treatment of GDM and related outcomes of mother and child. Metformin is used as a tool to reduce insulin resistance, the underlying cause of GDM. In the POEM study, the effects of metformin on top of standard of care versus standard of care alone in GDM are compared during pregnancy until 6 weeks after delivery (Phase A), from 6 weeks until 1 year after delivery (Phase B) and from 1 until 20 years after delivery (Phase C) with specified objectives reflected by well-defined clinically relevant endpoints.
研究设计
- 分配方式
- Randomized
- 主要目的
- Randomization
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 64 years（0-17 Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Pregnant women with GDM defined as a FPG ≥ 5,3 mmol/l and/or an OGTT with a PG ≥ 7,8 mmol/l, two hours after the oral intake of 75 gram glucose
- •Written informed consent
- •Age 18-45 years
- •Gestational age at inclusion 16-34 weeks
- •HbA1c at inclusion ≤ 48 mmol/mol (6.5% Hb)
排除标准
- •Diabetes mellitus before pregnancy, except previous GDM
- •Proteinuria (UACR > 35 mg/mmol) at screening (UTI excluded)
- •Malignancy during the last 5 years before inclusion, except non-melanoma skin cancer
- •Psychiatric and/or mood disorder potentially affecting compliance of treatment
- •Chronic liver disease and/or ASAT and/or ALAT > 3x ULN
- •Chronic renal failure with a GFR < 45 ml/min/1.73m2
- •Chronic pulmonary failure with hypoxia
- •Significantly uncontrolled hypertension – SBP > 160 mm Hg despite medical treatment
- •Chronic treatment with oral corticosteroids
- •Intolerance for metformin and/or earlier use of metformin in this pregnancy
- •Membership of the POEM study group
- •Severe foetal anomaly at inclusion – like major neural tube and/or cardiac malformation
- •Ruptured membranes
- •Multiple pregnancy
- •Bariatric surgery in medical history
- •Hyperemesis gravidarum
结局指标
主要结局
Phase A: GDM Outcome Score (= GOS), an ordinal variable (range 0-8) per pregnancy: (1) pregnancy related hypertension, including pre-eclampsia and eclampsia, (2) large for gestational age (LGA) at delivery (neonatal weight > 90th percentile), (3) premature delivery (< 37.0 weeks of gestation), (4) instrumental delivery, (5) caesarean delivery, (6) birth trauma, (7) neonatal hypoglycaemia (< 2.6 mmol/l), and (8) admission to the NICU.
Phase A: GDM Outcome Score (= GOS), an ordinal variable (range 0-8) per pregnancy: (1) pregnancy related hypertension, including pre-eclampsia and eclampsia, (2) large for gestational age (LGA) at delivery (neonatal weight > 90th percentile), (3) premature delivery (< 37.0 weeks of gestation), (4) instrumental delivery, (5) caesarean delivery, (6) birth trauma, (7) neonatal hypoglycaemia (< 2.6 mmol/l), and (8) admission to the NICU.
Phase B and Phase C have each three co-primary endpoints: maternal T2D, weight development in the mother, and weight development in the child.
Phase B and Phase C have each three co-primary endpoints: maternal T2D, weight development in the mother, and weight development in the child.
次要结局
- Phase A: each of these eight endpoints apart is a secondary endpoint.
- MOS (maternal outcome score): including Caesarean delivery, Pre-eclampsia/eclampsia/HELLP syndrome/gestational hypertension, Maternal mortality, Postpartum haemorrhage, Thrombosis (in pregnancy and/or childbed).
- NOS (neonatal outcome score): including Infant Respiratory Distress Syndrome (IRDS) needing nasal CPAP, optiflow, mechanical ventilation and/or surfactant replacement, stillbirth and neonatal death, preterm birth = birth before 37.0 weeks, dystocia of the shoulder during delivery, instrumental delivery, caesarean delivery, neonatal hypoglycaemia < 2.6 mmol/l, neonatal jaundice needing phototherapy, admission to NICU, Apgar score as a variable, Apgar score < 7 at 5 minutes, congenital anomaly
- Maternal weight, weight gain and change in body compostition (impedance)
- Maternal glycaemic control: FPG and glucose tolerance
- Maternale proteinuria
- Maternal insulin rescue and daily dose of insulin after failure of study drug
- Acceptability of treatment
- Maternal urinary tract infection
- Maternal metabolic varibales from venous sampling (please see protocol)
- Child: intra-uterine measurements by ultra-sonography
- Child: foetal weight at delivery
- Neonatal metabolic variables from umbilical cord
- Phase B/C: Diabetes & Prediabetes development, Weight development, Hypertension development, thrombotic and CVD incidents, development of any chronic disease
- Phase B/C: Growth and weight development, gonadal and gender development, puberty and maturation, eductional and intellectual development
研究者
Adriaan Kooy
Scientific
Bethesda Diabetes Research Center B.V.