A Randomised Placebo Controlled Trial of the Effectiveness of Early MEtformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects (EMERGE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 535
- 试验地点
- 2
- 主要终点
- Primary Composite Outcome
研究概览
简要总结
The overall objective of the EMERGE trial is to determine whether metformin + usual care, compared to placebo + usual care (introduced at the time of initial diagnosis of GDM), reduces a) the need for insulin use, or hyperglycemia (primary outcome measure); b) excessive maternal weight gain; c) maternal and neonatal morbidities and, d) cost of treatment for women with Gestational Diabetes Mellitus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide written informed consent
- •Participants aged 18-50
- •Pregnancy gestation up to 28 weeks (+ 6 days) confirmed by positive pregnancy test
- •Singleton pregnancy as determined by scan
- •Positive diagnosis of Gestational Diabetes Mellitus on a Oral Glucose Tolerance Test (OGTT) according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria if any one of the following are achieved: i) Fasting glucose >/= 5.1mmol/l and <7mmol/l, or ii) 1 hour post glucose load of >/=10mmol/l, or iii) 2 hour post glucose load of >/=8.5 mmol/l and <11.1mmo/l
- •Resident in the locality and intending to deliver within the trial site
排除标准
- •Participants who have an established diagnosis of diabetes (Type 1, Type 2, Monogenic or secondary)
- •Participants with a fasting glucose > 7mmol/l or a 2h value > 11.1 mmol/l
- •Multiple pregnancies (twins, triplets etc.) as determined by scan
- •Known intolerance to metformin
- •Known contraindication to the use of metformin which include: i) renal insufficiency (defined as serum creatinine of greater than 130 µmol/L or creatinine clearance <60 ml/min), ii) moderate to severe liver dysfunction (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) greater than 3 times the upper limit of normal, iii) shock or sepsis, and iv) previous hypersensitivity to metformin
- •Major congenital malformations or an abnormally deemed unsuitable for metformin by the site PI or attending consultant
- •Known small for gestational age (Small for gestational age (SGA) refers to foetal growth less than the 10th percentile (RCOG, 2014), or if foetal growth is deemed unsatisfactory by the treating obstetrician)
- •Known gestational hypertension or pre-eclampsia or ruptured membranes
- •Participants who have a history of drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements
- •Participants with significant gastrointestinal problems such as severe vomiting, Crohn's disease or colitis which will inadvertently affect absorption of the study drug
- •Participants with congestive heart failure or history of congestive heart failure
- •Participants with serious mental illness which would affect adherence to study medication or compliance with study protocol in the opinion of the investigator
- •Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
研究组 & 干预措施
Treatment
Participants randomised to the treatment arm will receive active metformin in addition to standard care. Metformin tablets will be titrated according to a dosing schedule to achieve the pre-specified glucose targets. Tablets will be in 500mg doses and will commence at 1 tablet per day (500mg) increasing to a maximum of 5 tablets per day (2500mg).
干预措施: Metformin Hydrochloride (Drug)
Control
Participants randomised to the placebo arm will receive placebo in addition to standard care. Placebo will be titrated according to the dosing schedule to achieve the pre-specified glucose targets. Placebo tablets will commence at 1 tablet per day and will be increased to a maximum of 5 tablets per day over 10 days as with the treatment group.
干预措施: Placebo (Other)
结局指标
主要结局
Primary Composite Outcome
时间窗: Enrolment through delivery, an average of 16 weeks.
The primary efficacy outcome was achieved if any participant experienced: * Insulin initiation * Fasting glucose value \>5.1 mmol/l at 32weeks or 38 weeks gestation.
Insulation of Insulin
时间窗: Enrolment through delivery, an average of 16 weeks.
Initiation of insulin treatment at any time up to delivery.
次要结局
- Insulin Dose Required(Enrolment through delivery, an average of 16 weeks.)
- Time to Insulin Initiation(Time to Insulin Initiation, from date of randomization until the date of delivery, an average of 16 weeks..)
- Postpartum Impaired Fasting Glucose(12 weeks post-partum)
- Insulin Initiated(Enrolment through delivery, an average of 16 weeks.)
- Fasting Hyperglycemia(Measured at 32 and 38 weeks' gestation.)
- Gestational Weight Gain(Enrolment through delivery, an average of 16 weeks.)
- Postpartum Impaired Glucose Tolerance(12 weeks postpartum)
- Postpartum Metabolic Syndrome(12 weeks postpartum)
- Gestational Age at Delivery(At delivery, an average of 16 weeks after enrolment)
- Mode of Delivery - Cesarian Delivery(At delivery, an average of 16 weeks after enrolment)
- Mode of Delivery - Emergency Cesarian Section(At delivery, an average of 16 weeks after randomization.)
- Mode of Delivery - Induced(At time of labor, an average of 16 weeks after enrolment.)
- Maternal Morbidity - Pregnancy-induced Hypertension(From enrolment through 6 weeks postpartum, an average of 22 weeks.)
- Maternal Morbidity - Pre-eclampsia(Enrolment through 6 weeks postpartum, an average of 22 weeks.)
- Maternal Morbidity - Antepartum Hemorrhage(From enrolment through delivery, an average of 16 weeks.)
- Maternal Morbidity - Postpartum Hemorrhage(From delivery through 6 weeks postpartum.)
- Birthweight(At birth)
- Birth Weight <2500g(At birth)
- Neonatal Head Circumference(At birth)
- Neonatal Height(At birth)
- Neonatal Abdominal Circumference(At birth)
- Neonatal Ponderal Index(At birth)
- Birth Weight >4000g(At birth)
- Birth Weight >90th Percentile(At birth)
- Birth Weight <10th Percentile(At birth)
- Neonatal Morbidity - Need for NICU Care(From birth until 6 weeks of life.)
- Neonatal Morbidity - Preterm Birth(At birth)
- Neonatal Morbidity - Respiratory Distress Syndrome Requiring Respiratory Support(From birth until 6 weeks of life.)
- Neonatal Morbidity - Jaundice Requiring Phototherapy(From birth until 6 weeks of life.)
- Neonatal Morbidity - Major Congenital Anomalies(From birth until 6 weeks of life.)
- Neonatal Morbidity - Apgar Score <7 at 5 Minutes(At 5 minutes after birth)
- Neonatal Morbidity - Neonatal Hypoglycemia(First hour of life.)
研究者
Fidelma Dunne
Prof. Fidelma Dunne
National University of Ireland, Galway, Ireland