Non-inferiority Between Acarbose and Prandial Insulin for the Treatment of Gestational Diabetes Mellitus: a Randomized Multicenter and Prospective Trial. ACARB-GDM Study.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 341
- 试验地点
- 1
- 主要终点
- Composite endpoint: birth weight ≥ 90th percentile for gestational age (large for gestational age: LGA) and/or neonatal hypoglycemia and/or shoulder dystocia and/or birth injury.
研究概览
简要总结
Caring for women with gestational diabetes mellitus (GDM) is very time-consuming. Therapeutic strategy includes dietary and lifestyle measures and additional insulin therapy for 15 to 40% of the women with GDM if the glycemic targets are not achieved after a period of 1 to 2 weeks of diet. Insulin therapy is imperfect for the following main reasons: need for education (i.e. subcutaneous administration, dose titration), hypoglycemia and weight gain, limited acceptance and high cost. Psychosocial deprivation is associated with more cases of GDM and health accessibility may be unequal.
Glucosidase inhibitors (acarbose) reduce intestinal absorption of starch and reduce the rate of complex carbohydrate digestion. It mainly lowers postprandial glucose values and is used in type 2 diabetes for a long time. Less than 2% of a dose is absorbed as active drug in adults, with 34% of the metabolites found in the systemic circulation. Doses of up to 9 and 32 times the human dose were not teratogenic in pregnant rats or rabbits. Limited but reassuring data during pregnancy are available. Acarbose was well tolerated (little gestational weight gain, no hypoglycemia) with digestive discomfort in some women, balanced by treatment satisfaction as compared with insulin injections. Our hypothesis is that treatment aiming to control postprandial glucose values with acarbose as compared with prandial insulin injection will be as efficient and safe, but more convenient and less expensive.
详细描述
Phase III study. Prospective, multicenter, non-inferiority, randomized, open-labelled and controlled study with two arms.
- In the 37 participating hospitals: selection of women with GDM who have unmet post prandial glycemic targets between 14 and 37 (+6 days) weeks of amenorrhea after at least 7 days of dietary and lifestyle measures. They may be treated with basal insulin to control pre prandial glucose values.
- Explanation of protocol, with signature of consent in case of acceptation.
- Randomization
. Experimental group: The women will receive acarbose with a progressive increase of dose according to post prandial glucose values and digestive tolerance, with a maximal dose of 3 x 100 mg / day. The progressive titration of acarbose reduces gastro-intestinal side effects.
Patients who have not reached the glycemic targets at this highest tolerated dose for at least one meal will receive instead prandial insulin therapy for each meal, whereas acarbose will be stopped. Failure to reach post-prandial target will be defined as 3 or more post-prandial glycaemic values ≥ 1.20 g/L for a given meal in a week (3 values out of 7) after the two weeks of dose adjustment.
· Control group: The women will receive prandial insulin according to usual practice (routine care according to French recommendations): before each meal, with dose titration according to post prandial values.
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
- None
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
- •Age ≥ 18 years
- •Singleton pregnancy
- •GDM diagnosed during pregnancy according to IADPSG criteria
- •Self-monitoring of blood glucose
- •After at least 7 days of dietary and lifestyle measures, unreached post-prandial glucose control
- •14-37 (+ 6 days) amenorrhea weeks at the time of randomization
- •Signed informed consent
排除标准
- •Prandial insulin use before randomization during this pregnancy
- •Use of other oral hypoglycemic agents during this pregnancy
- •Multiple pregnancy
- •Known hepatic insufficiency
- •Long time corticosteroid treatment
- •Pre-existing diabetes in pregnancy
- •Overt diabetes diagnosed during pregnancy (IADPSG criteria)
- •Lack of Social Insurance
- •Insufficient understanding
- •Participant in another investigational drug study at inclusion visit
- •Contraindications of acarbose
- •Fetal malformation diagnosed by previous fetal ultrasound
研究组 & 干预措施
acarbose
The women will receive acarbose with a progressive increase of dose according to post prandial glucose values and digestive tolerance, with a maximal dose of 3 x 100 mg /day
干预措施: Acarbose (Drug)
prandial insulin
The women will receive prandial insulin according to usual practice (routine care according to French recommendations): before each meal, with dose titration according to post prandial values.
干预措施: Prandial insulin (Drug)
结局指标
主要结局
Composite endpoint: birth weight ≥ 90th percentile for gestational age (large for gestational age: LGA) and/or neonatal hypoglycemia and/or shoulder dystocia and/or birth injury.
时间窗: At delivery
LGA defined as birth weight greater than the 90th percentile for a standard French population * Neonatal hypoglycemia defined as at least a blood glucose value less than a 2.0 mmol/l during the two first days of life; * Shoulder dystocia, defined as vaginal cephalic delivery that requires additional obstetric manoeuvres to deliver the fetus after the head has delivered and gentle traction has failed. We will only consider rotational maneuvers such as Rubin II or Woods corkscrew or Jaquemier maneuvers * Birth injury defined as plexus injury or clavicle fracture.
次要结局
- GLUCOSE CONTROL: HbA1c(At delivery)
- Neonatal complications : Low Apgar score(At delivery)
- Side effects of drugs : Maternal hypoglycemia(during the 7 months of treatment)
- Results of oral glucose tolerance test and HbA1c measurement(3 months after delivery)
- Conservation of serum and plasma; cord fluid. The samples may be used for further analyses ancillary studies and which could be beneficial for GDM care based on evolution in scientific knowledge.(within 10 years after the end of the study)
- GLUCOSE CONTROL: Capillary glucose levels(From two weeks after inclusion : 14 and 37 (+6 days) weeks of amenorrhea to delivery)
- Neonatal complications : Birth weight and height,(At delivery)
- Acceptance/satisfaction of two strategies : -Quality of life -Satisfaction questionnaires(At delivery)
- Neonatal complications : Small for gestational age infant(At delivery)
- Maternal complications : Preeclampsia(From two weeks after inclusion to delivery)
- Maternal complications : Pregnancy-induced hypertension(From two weeks after inclusion : 14 and 37 (+6 days) weeks of amenorrhea to delivery)
- Neonatal complications : Neonatal respiratory distress syndrome(At delivery)
- Neonatal complications : Intrauterine fetal or neonatal death;(From two weeks after inclusion to delivery)
- GLUCOSE CONTROL: Need for and dose/day of basal and prandial insulin in both arms(At delivery)
- Neonatal complications : Preterm delivery(At delivery)
- Gastro-intestinal side effects(from two weeks after inclusion : 14 to 36 weeks of gestation to delivery)
- Infant anthropometrics.(At month 1, month 2 and month 3)