NCT02518594已完成3 期
A Randomized Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix
The George Washington University Biostatistics Center29 个研究点 分布在 1 个国家目标入组 1,311 人开始时间: 2015年11月13日最近更新:
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,311
- 试验地点
- 29
- 主要终点
- Number of Participants With Delivery or Fetal Loss of Either Twin Prior to 35 Weeks Gestation
研究概览
简要总结
This protocol outlines a randomized trial of 630 women evaluating the use of micronized vaginal progesterone or pessary versus control (placebo) to prevent early preterm birth in women carrying twins and with a cervical length of less than 30 millimeters.
详细描述
This protocol outlines a randomized trial of 630 women evaluating the use of micronized vaginal progesterone or pessary versus control (placebo) to prevent early preterm birth in women carrying twins and with a cervical length of less than 30 millimeters.
Multiple gestation increases the risk of preterm delivery. Babies born preterm have increased rates of neonatal mortality and long-term neurodevelopmental morbidities. Short cervical length is known to be an important risk factor for spontaneous preterm birth and to occur more frequently in women with a twin gestation. Although there is no evidence that progesterone reduces the risk of preterm birth in multifetal gestation, there is evidence that progesterone reduces the risk of prematurity in singleton gestations complicated with a short cervix. The Arabin pessary has also been shown to reduce the risk of preterm birth among singletons with a short cervix, and in a secondary subgroup analysis of a recent study of the use of pessary in multiple gestations, women with a cervical length < 25th percentile had a significantly reduced risk of the primary composite neonatal adverse outcome. Secondary analysis of studies of vaginal progesterone in multiple gestation with a short cervix also suggest a possible beneficial effect on preterm delivery.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants and care providers will be blinded to active study drug vs. placebo.
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Twin gestation with cardiac activity in both fetuses. Higher order multifetal gestations reduced to twins, either spontaneously or therapeutically, are not eligible unless the reduction occurred by 13 weeks 6 days project gestational age.
- •Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
- •Cervical length on transvaginal examination of less than 30 mm by a study certified sonographer.
排除标准
- •Cervical dilation (internal os) 3 cm or greater on digital examination or evidence of prolapsed membranes beyond the external cervical os either at the time of the qualifying cervical ultrasound examination or at a cervical exam immediately before randomization. There is no lower threshold of cervical length measurement threshold on ultrasound that is an exclusion criterion.
- •Monoamniotic gestation, due to increased risk of adverse pregnancy outcome
- •Twin-twin transfusion syndrome, due to increased risk of adverse pregnancy outcome
- •Evidence of severe IUGR (intrauterine growth restriction) (<5th percentile for gestational age) in either fetus
- •Fetal anomaly in either twin or imminent fetal demise. This includes lethal anomalies, or anomalies that may lead to early delivery or increased risk of neonatal death e.g., gastroschisis, spina bifida, serious karyotypic abnormalities). An ultrasound examination from 14 weeks 0 days to 23 weeks 6 days by project EDC (estimated date of conception) must be performed prior to randomization to evaluate the fetuses for anomalies.
- •Placenta previa, because of risk of bleeding and high potential for indicated preterm birth
- •Active vaginal bleeding greater than spotting at the time of randomization, because of potential exacerbation due to pessary placement.
- •Symptomatic, untreated vaginal or cervical infection, also because of potential exacerbation due to pessary placement. Patients may be treated and if subsequently asymptomatic, randomized.
- •Active, unhealed herpetic lesion on labia minora, vagina, or cervix due to the potential for significant patient discomfort or increasing genital tract viral spread. Once lesion(s) heal and the patient is asymptomatic, she may be randomized. History of herpes is not an exclusion.
- •Rupture of membranes due to likelihood of pregnancy loss and preterm delivery as well as the risk of ascending infection which could be increased with pessary placement
- •More than six contractions per hour reported or documented prior to randomization. It is not necessary to place the patient on a tocodynamometer
- •Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate, or uterine septum not resected) due to increased risk of preterm delivery which is unlikely to be affected by progesterone
- •Any fetal/maternal condition which would require invasive in-utero assessment or treatment, for example significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia
- •Major maternal medical illness associated with increased risk for adverse pregnancy outcome or indicated preterm birth (treated hypertension requiring more than one agent, pre-gestational treatment for diabetes prior to pregnancy, chronic renal insufficiency failure defined by creatinine >1.4 mg/dL, carcinoma of the breast, conditions treated with chronic oral glucocorticoid therapy. Specifically, patients with seizure disorders, HIV, and other medical conditions not specifically associated with an increased risk of indicated preterm birth are not excluded. Prior cervical cone/LOOP/LEEP is not an exclusion criterion.
- •Planned cerclage or cerclage already in place since it would preclude placement of a pessary
- •Planned indicated delivery prior to 35 weeks
- •Planned or actual progesterone treatment of any type or form after 15 weeks 6 days during the current pregnancy
- •Allergy to progesterone, silicone, or excipients in the study drug, including peanuts or peanut oil in the study drug or placebo
- •Known, suspected or history of breast cancer because breast cancer is a contraindication to the active study medication.
- •Known liver dysfunction or disease because liver disease is a contraindication to the active study medication.
- •Participation in another interventional study that influences gestational age at delivery or neonatal morbidity or mortality
- •Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, do not have to be excluded.
- •Prenatal care or delivery planned elsewhere unless the study visits can be made as scheduled and complete outcome information can be obtained
研究组 & 干预措施
Placebo
Placebo Comparator
placebo capsule
干预措施: Placebo (Drug)
Arabin Pessary
Active Comparator
Arabin Pessary
干预措施: Arabin Pessary (Device)
Progesterone
Active Comparator
vaginal progesterone capsule
干预措施: Vaginal progesterone (Drug)
结局指标
主要结局
Number of Participants With Delivery or Fetal Loss of Either Twin Prior to 35 Weeks Gestation
时间窗: From randomization to 35 weeks gestation (a period of up to 19 weeks)
Number of Participants who had preterm delivery or fetal loss of either twin prior to 35 weeks gestation
次要结局
- Days From Randomization to Delivery (or Fetal Demise)(Randomization to delivery (a period of up to 26 weeks))
- Gestational Age at Delivery or Fetal Death(Randomization to delivery (a period of up to 26 weeks))
- Number of Participants With Preterm Delivery or Fetal Demise of Either Twin Prior to 28 Weeks Gestation(From randomization to up to 28 weeks gestation (a period if up to 12 weeks))
- Number of Participants With Preterm Delivery or Fetal Demise of Either Twin Prior to 32 Weeks Gestation(From randomization to 32 weeks gestation (a period of up to 16 weeks))
- Number of Participants With Preterm Delivery or Fetal Demise of Either Twin Prior to 37 Weeks Gestation(randomization to 37 weeks gestation (a period of up to 21 weeks))
- Number of Participants With Spontaneous Preterm Delivery < 32 Weeks Gestation(randomization to 32 weeks gestation (a period of up to 16 weeks))
- Number of Participants With Spontaneous Preterm Delivery < 35 Weeks Gestation(randomization to 35 weeks gestation (a period of up to 19 weeks))
- Number of Participants With Indicated Preterm Delivery for < 35 Weeks(randomization to 35 weeks gestation (a period of up to 19 weeks))
- Number of Participants With Cesarean Delivery(Randomization to delivery (a period of up to 26 weeks))
- Number of Fetal, Neonatal or Infant Deaths(From randomization to up to 28 days post birth (a period of up to 30 weeks))
- Number of Neonates Small for Gestational Age < 5th Percentile(randomization to delivery (a period of up to 26 weeks))
- Number of Neonates With the Composite Neonatal Outcome(Birth to neonatal discharge or death, whichever is first (up to 70 weeks))
- Number of Neonates Admitted to Intensive Care (NICU) or Intermediate Care(Birth to the time of NICU or Intermediate Care Admission, whichever came first (a maximum of 10 days))
- Length of Neonatal Hospital Stay in Days(admission to hospital discharge (a median of 12 days with a maximum of 490 days))
- Length of Stay in Neonatal Intensive Care (NICU) or Intermediate Care in Days(admission to discharge from NICU or intermediate care (a median of 28 days, with a maximum of 491 days))
研究者
研究点 (29)
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