Metformin in Women With Type 2 Diabetes in Pregnancy Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- A composite of: pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, and NICU admission > 24 hours.
研究概览
简要总结
Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, however despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, in addition to treatment with insulin, will help with blood sugar control, lower the dose of insulin needed, lower weight gain, and improve baby outcomes.
详细描述
Type 2 diabetes in pregnancy is increasing in prevalence and these women continue to face increased rates of adverse maternal and fetal outcomes. The investigators hypothesize that metformin use, as an adjunct to insulin, will decrease these adverse outcomes by reducing maternal hyperglycemia, high maternal insulin doses, excessive maternal weight gain and gestational hypertension/pre-eclampsia, all of which should reduce perinatal and neonatal mortality and morbidity. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. This study is an randomized controlled trial (RCT) that adds metformin to insulin, and is a double-blind, placebo-controlled RCT. The investigators believe that neither metformin alone nor insulin alone will effectively treat this population, and therefore our design, which includes the addition of metformin to insulin, will be the most relevant to our patients.
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 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women who are between of 18-45 years of age.
- •(i). Women diagnosed with type 2 diabetes prior to pregnancy, OR (ii). Women with undiagnosed type 2 diabetes diagnosed prior to 20 weeks gestation, defined as women presenting with gestational diabetes before 20 weeks gestation with various combinations, as per Canadian Diabetes Association, including:
- •2 fasting glucose ≥ 7.0 mmol/L, or
- •2 HbA1c of ≥0.065 (6.5%) performed in a laboratory using a method that is standardized to the Diabetes Control and Complications Trial (DCCT) assay, or
- •1 fasting glucose ≥7.0 mmol/L and 1 HbA1c ≥ 0.065 (6.5%) performed in a laboratory using a method that is standardized to the DCCT assay, or
- •1 fasting glucose ≥ 7.0 mmol/L and 1 two hour (2 hr) ≥ 11.1 on a 75 g Oral Glucose Tolerance Test (OGTT), or
- •1 HbA1C ≥0.065 (6.5%) performed in a laboratory using a method that is standardized to the DCCT assay and 1 two hour (2 hr) ≥ 11.1 on a 75 g OGTT.
- •Pregnancy gestation between 6+0-22+6 weeks.
- •Live singleton fetus.
排除标准
- •Women who are not on insulin. Women who are on oral hypoglycemic agents will be taken off at the start of the trial and started on insulin prior to randomization.
- •Diabetes diagnosed after 20 weeks gestation.
- •Type 1 diabetes.
- •Known intolerance to metformin.
- •Contraindications to metformin use 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 (defined as liver enzymes (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.
- •f. Women with significant gastrointestinal problems such as severe vomiting requiring IV fluids or hospitalization, or active Crohn's or colitis.
- •g. Previous participation in the trial. h. Women who have a fetus with a known potentially lethal anomaly will be excluded. Information regarding congenital anomalies diagnosed after randomization will be recorded.
- •i. Known higher order pregnancies (twins, triplets, etc). These women will be excluded as they have a higher rate of adverse outcomes and we want to avoid any inequalities if they are unequally distributed between the groups.
- •j. Presence of acute or chronic metabolic acidosis, including diabetic ketoacidosis.
- •k. History of diabetic ketoacidosis or history of lactic acidosis. l. Presence of excessive alcohol intake, acute or chronic. m. Presence of congestive heart failure or history of congestive heart failure.
研究组 & 干预措施
Metformin
干预措施: Metformin (Drug)
Placebo
干预措施: Placebo Comparator (Drug)
结局指标
主要结局
A composite of: pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, and NICU admission > 24 hours.
时间窗: conception to 28 days after birth
次要结局
- Fetal fat mass(Up to 7 days after birth)
- Pregnancy loss(Up to 40 weeks gestation)
- Neonatal hypoglycemia(NICU admission >24 hours)
- NICU admission >24 hours(NICU admission >24 hours)
- Large for gestational age (LGA) infants(Up to 24 hours after birth)
- Preterm birth(Up to 37 weeks gestation)
- Respiratory distress(within 72 hours after birth)
- Maternal weight gain(Up to 40 weeks gestation)
- Maternal insulin doses(Up to 40 weeks gestation)
- Pre-eclampsia, and/or gestational hypertension(Up to 40 weeks gestation)
- Sepsis(Up to 28 days after birth)
- Maternal glycemic control as measured by HbA1c and capillary glucose measurements.(Up to 40 weeks gestation)
- Maternal hypoglycemia(Up to 40 weeks gestation)
- Cord blood gases pH <7.0(Within 4 hours of birth)
- Hyperinsulinemia as measured by elevated cord blood C-peptide(Within 4 hours of birth)
- Hyperbilirubinemia(First 7 days of life)
- Number of hospitalizations(Up to 40 weeks gestation)
- Rate of caesarean-section(Up to 40 weeks gestation)
- Duration of hospital stay for infant.(Up to 28 days after birth)
- Birth Injury(Up to 7 days after birth)
- Shoulder dystocia(At delivery)