Induction of Labor at 40 Weeks Versus Expectant Management Until 41 Weeks in Women With A1 Gestational Diabetes Mellitus: A Multicenter, Open-Label, Superiority Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 1,500
- 试验地点
- 1
- 主要终点
- Cesarean delivery rate
研究概览
简要总结
This multicenter, open-label, superiority randomized controlled trial will evaluate whether delaying planned induction from 40 weeks to 41 weeks improves delivery outcomes in women with A1 gestational diabetes mellitus (A1 GDM). The study is designed to enroll 1,500 eligible women (750 per group), all of whom are planned for vaginal delivery.
Eligible participants are women aged 18-40 years with singleton pregnancy and who are primiparous. GDM will be diagnosed using OGTT at 24-28 weeks, and participants must meet criteria for A1 GDM, meaning blood glucose is controlled with diet and exercise only (no insulin or other glucose-lowering medications during pregnancy). After providing written informed consent, participants will be randomized 1:1 to one of two pre-specified induction strategies.
Control group (planned induction at 40 weeks): Participants will have planned induction at 40+0 weeks (time window 39+6 to 40+0). If spontaneous labor occurs before or during the window, obstetric management will follow routine clinical practice. If labor has not started by the end of the window, induction will be performed according to the protocol.
Intervention group (expectant management until 41 weeks): Participants will be managed expectantly until 41+0 weeks with planned induction in the 41+0 to 41+1 weeks window. If spontaneous labor occurs before or during the window, routine obstetric management will be used. If labor has not started by the end of the window, induction will be performed according to the protocol.
Participants will be followed from randomization until delivery and hospital discharge, with selected outcomes followed up to postpartum day 42. The primary outcome is the cesarean delivery rate. Secondary outcomes include maternal outcomes such as postpartum hemorrhage and other obstetric complications, neonatal/perinatal outcomes including perinatal death, and need for respiratory support, as well as selected health-economic and patient-reported outcomes. All participating centers will apply standardized procedures for screening, monitoring, induction methods, and data collection. An independent Data and Safety Monitoring Board (DSMB) and a blinded Clinical Endpoint Committee will monitor safety and validate the primary outcome.
The trial is expected to be completed within approximately 18 months after initiation of recruitment, and the results will provide high-quality evidence to inform timing of delivery for women with A1 GDM in China.
详细描述
（A）Study Title The WAIT trial: Induction of Labor at 40 Weeks versus Expectant Management until 41 Weeks in Women with A1 Gestational Diabetes Mellitus: A Multicenter, Open-Label, Superiority Randomized Controlled Trial.
（B）Background and Rationale Gestational diabetes mellitus (GDM) is increasingly common, affecting approximately 12-18% of pregnancies. Hyperglycemia may increase risks for both mothers and infants, including vascular dysfunction, hypertensive disorders, infections, postpartum hemorrhage, polyhydramnios, fetal macrosomia, congenital anomalies, and stillbirth. GDM is also associated with long-term metabolic consequences, including persistent insulin resistance and impaired β-cell function, which increase the risk of type 2 diabetes after pregnancy.
Although induction of labor may affect maternal and neonatal outcomes, the optimal timing of delivery in women with A1 GDM remains uncertain, and recommendations in guidelines are inconsistent. Chinese guidelines recommend induction at 40-41 weeks; however, the evidence level for this recommendation is C. Studies on the timing of induction in GDM are mostly observational, and their findings are heterogeneous. Notably, randomized controlled trial evidence specifically in women with A1 GDM comparing planned induction at 40 weeks with induction after expectant management until 41 weeks is currently limited.
In China, cesarean delivery rates remain high. Reducing unnecessary cesarean delivery is important for public health, but any change in timing must be weighed against maternal and neonatal safety. Therefore, this trial primarily uses the cesarean delivery rate as the primary outcome, and also evaluates maternal and neonatal safety outcomes and health-economic impacts to assess net clinical benefit.
（C）Objectives Primary objective: To determine whether planned induction at 41 weeks (after expectant management from 40 weeks) reduces the cesarean delivery rate compared with planned induction at 40 weeks in women with A1 GDM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Aged 18-40 years;
- •Singleton pregnancy;
- •Nulliparous;
- •Diagnosed with gestational diabetes mellitus (GDM) by oral glucose tolerance test (OGTT) at 24-28 weeks of gestation;
- •At screening/enrollment, classified as A1 GDM, defined as good glycemic control after exercise counseling and nutritional management. Both of the following criteria must be met: (1) No use of insulin or other glucose-lowering medications during pregnancy up to screening/enrollment, verified through medication orders in the hospital information system (HIS); and (2) The clinician assesses overall glycemic control during pregnancy as meeting target and explicitly documents A1 GDM in the outpatient medical record.
- •Provides written informed consent.
排除标准
- •Maternal factors: signs of labor; prelabor rupture of membranes; history of cesarean delivery or uterine surgery (e.g., myomectomy); clinically assessed pelvic contraction (e.g., pelvic outlet diameter ≤7.5 cm); cervical cerclage during the current pregnancy; planned cesarean delivery or any known contraindication to vaginal delivery; or severe pregnancy-related complications or comorbidities considered by the investigator to preclude tolerance of vaginal delivery, such as severe heart disease complicating pregnancy, intrahepatic cholestasis of pregnancy, hypertensive disorders of pregnancy, psychiatric disorders/cognitive impairment, autoimmune diseases, or severe anemia.
- •Fetal factors: non-cephalic presentation; intrauterine fetal demise; fetal distress; fetal structural malformations or chromosomal abnormalities; fetal growth restriction (ultrasound-estimated fetal weight below the 10th percentile); or large-for-gestational-age fetus (ultrasound-estimated fetal weight above the 90th percentile).
- •Amniotic fluid factors: oligohydramnios, defined as an amniotic fluid index (AFI) ≤5 cm or a maximum vertical pocket (MVP) ≤2 cm; or polyhydramnios, defined as an AFI ≥25 cm or an MVP ≥8 cm.
- •Placental factors: placenta previa, placenta accreta spectrum, vasa previa, or similar conditions.
- •Medication-related contraindications: contraindications to induction agents such as misoprostol or oxytocin, including asthma, glaucoma, a scarred uterus, or drug allergy/hypersensitivity.
研究组 & 干预措施
Experimental Arm
Pregnant women in this arm will receive expectant management until 41+0 weeks (time window: 41+0-41+1 weeks). Routine obstetric care will be provided if spontaneous labor occurs. Labor induction will be conducted for those without spontaneous labor.
干预措施: Timing of Planned Delivery (Behavioral)
Control Arm
Pregnant women in this arm will receive planned labor induction at 40+0 weeks (time window: 39+6-40+0 weeks). Routine obstetric care will be provided if spontaneous labor occurs. Labor induction will be conducted for those without spontaneous labor.
干预措施: Timing of Planned Delivery (Behavioral)
结局指标
主要结局
Cesarean delivery rate
时间窗: From date of randomization until delivery, assessed up to 42 days postpartum
The proportion of randomized participants who undergo cesarean delivery from randomization until delivery, calculated as: number of participants undergoing cesarean delivery / number of randomized participants × 100%. Cesarean delivery includes elective cesarean delivery, intrapartum cesarean delivery, non-elective cesarean delivery before labor onset for medical indications, including emergency cesarean delivery, and other cesarean deliveries performed for medical indications. This outcome will be derived from the "mode of delivery" field in the case report form. Cesarean delivery indications include failed induction of labor, dystocia or abnormal labor progression, nonreassuring fetal status, and other medical indications, as specified in the case report form.
次要结局
- Postpartum blood loss(From delivery through 24 hours postpartum)
- Macrosomia rate(At birth)
- Perinatal mortality(From date of randomization until 28 days after birth)
- Neonatal respiratory support(From date of birth until neonatal hospital discharge, assessed up to 42 days postpartum)
- Other secondary maternal outcomes(From date of randomization until 42 days postpartum, as applicable.)
- Other secondary fetal/neonatal outcomes(From date of randomization until 42 days postpartum, as applicable)
- Average daily medical cost(From hospital admission until hospital discharge, assessed up to 42 days postpartum)
- Total medical cost(From hospital admission until hospital discharge, assessed up to 42 days postpartum)
- Incremental cost-effectiveness ratio(From hospital admission until hospital discharge, assessed up to 42 days postpartum)