Cervical Cerclage With Vaginal Progesterone Versus Vaginal Progesterone Only for Preterm Birth Prevention in Women With a Singleton Pregnancy and a Short Cervical Length: a Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 328
- 试验地点
- 1
- 主要终点
- Time from randomization to delivery
研究概览
简要总结
This study compares the effectiveness of cervical cerclage with vaginal progesterone to vaginal progesterone only for the prevention of preterm birth in women with a singleton pregnancy and a short cervical length. Participants will be randomly assigned in a 1:1 ratio to receive cerclage plus progesterone or progesterone only.
详细描述
This open-label, multi-center, randomized controlled trial aims to compare the effectiveness of cervical cerclage with vaginal progesterone (the combined therapy group) to vaginal progesterone only (the progesterone-only group) for the prevention of preterm birth in women with a singleton pregnancy and a cervical length ≤ 25mm.
After written informed consent, women will be randomly assigned in a 1:1 ratio to receive a cervical cerclage with vaginal progesterone or vaginal progesterone only. Randomization will be carried out by entering participant details into HOPE Epi® (a web portal of HOPE Research Center, My Duc Hospital). Treatment allocation will be assigned according to a computer-generated randomization list stored in the online system, with a permuted random block size of 2, 4, or 6. Blinding will not be possible due to the nature of interventions. However, neonatologists assessing the neonates will be unaware of treatment allocation. Apart from randomization, participants will be monitored and treated according to local protocol.
All women at 16 0/7 to 24 0/7 weeks' gestation with a singleton pregnancy will undergo cervical length measurement and digital examination at screening routinely. Women with a cervical length ≤25 mm will be eligible for the study. Eligible women will further undergo a speculum examination to assess the feasibility of treatment with either cervical cerclage or vaginal progesterone and to exclude premature rupture of the membranes, acute vaginitis, and cervicitis. Only women in whom the clinician assesses both treatments as feasible will be randomized.
Women allocated to a combined therapy group will receive the intervention according to local protocol within a week after randomization. Briefly, cervical cerclage (McDonald technique) will be performed in the operation theatre. From the same day of undergoing cerclage, participants will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200mg, Actavis, United Kingdom), once daily at bedtime. Participants will be asked to record their drug application in a participant diary sheet.
Women allocated to the progesterone-only group will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200mg, Actavis, United Kingdom), once daily at bedtime. Participants will be asked to record their drug application in a participant diary sheet.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Maternal age ≥18 years
- •Singleton pregnancy
- •Cervical length ≤ 25 mm, measured by TVS at the second-trimester ultrasonography (16 0/7 - 24 0/7 weeks of gestation)
- •Not participating in any other study which has intervention on maternity or fetus
- •Provision of written informed consent as shown by a signature on the participant consent form.
排除标准
- •Cervical dilation with visible amniotic membranes or amniotic membranes prolapsed into the vagina
- •Major congenital abnormalities of the fetus
- •Intrauterine fetal demise
- •Presence of severe vaginal discharge*
- •Presence of vaginitis or cervicitis*
- •Presence of vaginal bleeding*
- •Placenta previa or vasa previa
- •Preterm premature rupture of membranes
- •Preterm labor without ruptured membrane at the time of screening
- •Suspected chorioamnionitis
- •Unable to undergo cerclage
- •Cerclage in place
- •Allergy to progesterone
- •(*Women with acute cervicitis, vaginitis or severe vaginal discharge are eligible once they have been treated and if they have a CL ≤25 mm between 16 0/7 - 24 0/7 weeks of gestation.)
研究组 & 干预措施
Combined therapy group (cervical cerclage plus vaginal progesterone)
Women will be receiving the cervical cerclage according to local protocol within a week after randomization, using the McDonald technique.
Within one day after the procedure, they will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200mg, Actavis, United Kingdom), once daily at bedtime. Participants will be asked to record their drug application in a patient diary sheet.
干预措施: Cervical cerclage (Procedure)
Combined therapy group (cervical cerclage plus vaginal progesterone)
Women will be receiving the cervical cerclage according to local protocol within a week after randomization, using the McDonald technique.
Within one day after the procedure, they will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200mg, Actavis, United Kingdom), once daily at bedtime. Participants will be asked to record their drug application in a patient diary sheet.
干预措施: Vaginal progesterone (Drug)
Progesterone only group
Women allocated to the progesterone only group will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200mg, Actavis, United Kingdom), once daily at bedtime. Participants will be asked to record their drug application in a patient diary sheet.
干预措施: Vaginal progesterone (Drug)
结局指标
主要结局
Time from randomization to delivery
时间窗: From date of randomization until the date of delivery
Number of days between randomization and delivery
次要结局
- 5-min Apgar score(5 min after birth)
- Onset of labor(At birth)
- Use of Post cerclage antibiotics(Within one week after the cerclage procedure)
- Live birth(At birth)
- Length of stay in the neonatal intensive care unit(Up to 28 days after estimated due date)
- 1-min Apgar score(1 min after birth)
- Composite poor neonatal outcomes (major sencondary endpoint)(From 20 weeks of gestation to 28 days after estimated due date)
- Miscarriage <22 weeks (late miscarriage)(From date of randomization to 22 weeks of gestation)
- Preterm birth <24 weeks, <28 weeks, <32 weeks, <34 weeks and <37 weeks of gestation(At delivery)
- Mode of delivery(At birth)
- All stillbirth(After 20 weeks of gestation)
- Early stillbirth(≥ 20 weeks and < 28 weeks of gestation)
- Admission to neonatal intensive care unit(At birth and up to 28 days after birth)
- Gestational age at delivery(At delivery)
- Use of tocolytic drugs(From 24 0/7 to 33 6/7 weeks' gestation)
- Length of maternal admission for labour(Up to 2 weeks after birth)
- Chorioamnionitis(From randomization to delivery)
- Birthweight <1500 g(At birth)
- Birthweight <2500 g(At birth)
- Late stillbirth(After 28 weeks of gestation)
- Neonatal sepsis(Up to 28 days after estimated due date)
- Spontaneous preterm birth <24 weeks, <28 weeks, <32 weeks, <34 weeks and <37 weeks of gestation(At delivery)
- Iatrogenic preterm birth <24 weeks, <28 weeks, <32 weeks, <34 weeks and <37 weeks of gestation(At delivery)
- Use of antenatal corticosteroids(From 24 0/7 to 33 6/7 weeks' gestation)
- Use of MgSO4 for neuroprotection(From 24 0/7 to 31 6/7 weeks' gestation)
- Fetal growth restriction(From randomization to delivery)
- Maternal mortality(From randomization to during pregnancy and childbirth or within 42 days of termination of pregnancy)
- Maternal side effects(From date of randomization until delivery)
- Intraventricular haemorrhage II B or worse(Up to 28 days after estimated due date)
- Perinatal death(From 20 weeks of gestation to the first 28 days of life after delivery)
- Preterm premature rupture of membranes(From randomization to before 37 weeks of gestation)
- Total length of admission for threatened preterm labor(From 22 0/7 to 36 6/7 weeks of gestation)
- Birthweight(At birth)
- Congenital anomalies(After randomization to at birth)
- Respiratory distress syndrome(Up to 28 days after estimated due date)
- Neonatal death(Within the first 28 days of life after delivery)
- Necrotizing enterocolitis(Up to 28 days after estimated due date)