TOTAL TRIAL: Randomized Trial of Fetoscopic Endoluminal Tracheal Occlusion (FETO) Versus Expectant Management During Pregnancy in Fetuses With Left-Sided and Isolated Congenital Diaphragmatic Hernia and Moderate Pulmonary Hypoplasia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Proportion of Neonate Survival at Discharge From Hospital
研究概览
简要总结
This trial will test whether temporary fetoscopic endoluminal tracheal occlusion (FETO) rather than expectant management during pregnancy, followed by standardized postnatal management, increases survival at discharge and decreases oxygen need at 6 months in case of survival till discharge.
详细描述
This is a multi-center, non-blinded randomized controlled trial in fetuses with isolated moderate CDH, i.e. moderate lung hypoplasia (as determined by prenatal assessment of lung development). It essentially compares fetal therapy added to conventional postnatal care, versus expectant prenatal management during pregnancy followed by conventional postnatal care.
Enrollment:
Following completion of an inclusion/exclusion criteria checklist and obtaining informed consent, the subject will be randomized into two groups ("FETO" and "expectant").
Procedures:
Group I: Standardized postnatal care (expectant group): mothers will be expectantly managed during pregnancies and babies receive standardized postnatal care at a tertiary center used to manage babies with CDH. The recommendation is that they adhere to consensus guidelines published on the study website.
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 64 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18 years or more, who are able to consent,
- •Singleton pregnancy,
- •Chromosomally normal fetus,
- •Gestation at randomization prior to 31 weeks plus 5 days or so that occlusion is done at the latest on 31 weeks plus 6 days,
- •Fetus is estimated to have moderate pulmonary hypoplasia, defined prenatally as:
- •O/E LHR 25-34.9% (included; irrespective of the position of the liver) • O/E LHR 35-44.9% (included) with intrathoracic liver herniation as determined by ultrasound or MRI.
- •The O/E LHR will be determined by the FETO centers as follows:
- •Measurement of the contralateral lung area preferentially by the tracing method at the 4-chamber view of the heart; if by other method adjusted normative ranges must be used.
- •Measurement of the head circumference at the standard biparietal view of the head
- •The observed lung area: calculation of the LHR as the ratio of the measurements of the lung area to head circumference
- •The expected lung area is the lung area of a normal gestational age match, as determined by the head circumference of the index case in a normogram established for the same measurement method (tracing method in this case). A calculator for this will be available on the website of the study.
- •Calculation of the observed over expected lung area,
- •Acceptance of randomization and the consequences for the further management during pregnancy and thereafter, this includes the required observation following FETO surgery, which lasts up to 4 weeks after balloon is in place,
- •The patients must undertake the responsibility for either remaining close to, or at the FETO center, or being able to travel swiftly and within acceptable time interval to the FETO center until the balloon is removed. Intended postnatal treatment center must subscribe to suggested guidelines for "standardized postnatal treatment," and
- •Provide written consent to participate.
- •Fetus with no major anomalies that would impact the clinical course or outcomes.
排除标准
- •Maternal contraindication to fetoscopic surgery or severe medical condition in pregnancy that make fetal intervention risky,
- •Technical limitations precluding fetoscopic surgery, such as severe maternal obesity, uterine fibroids or potentially others, not anticipated at the time of writing this protocol,
- •Preterm labor, cervix shortened (<15 mm at randomization) or uterine anomaly strongly predisposing to preterm labor, placenta previa,
- •Patient age less than 18 years,
- •Psychosocial ineligibility, precluding consent,
- •Diaphragmatic hernia: right-sided or bilateral, major anomalies, isolated left-sided outside the O/E LHR limits for the inclusion criteria, and
- •Patient refusing randomization, to comply with required 4-week observation after balloon placement, or to comply with return to FETO center during the time period the airways are occluded or for elective removal of the balloon.
- •Patient allergic to latex.
研究组 & 干预措施
Standardized postnatal care (Expectant)
Mothers will be expectantly managed during pregnancies and babies receive standardized postnatal care at a tertiary center used to manage babies with CDH. The recommendation is that they adhere to consensus guidelines published on the study website.
干预措施: Standardized postnatal care (Other)
Prenatal Intervention (FETO)
Patients will undergo fetoscopic endoluminal tracheal occlusion and ideally prenatal reversal of the occlusion followed by standardized postnatal care as in the expectant . In this study FETO (where GoldBal2 detachable balloon and Baltaccidbpe100 Delivery Catheter are used) is to be done between 30 weeks plus 0 day and 31 weeks plus 6 days and removal of the balloon at 34 weeks plus 0 day to 34 weeks plus 6 days.
干预措施: GoldBal2 detachable balloon (Device)
Prenatal Intervention (FETO)
Patients will undergo fetoscopic endoluminal tracheal occlusion and ideally prenatal reversal of the occlusion followed by standardized postnatal care as in the expectant . In this study FETO (where GoldBal2 detachable balloon and Baltaccidbpe100 Delivery Catheter are used) is to be done between 30 weeks plus 0 day and 31 weeks plus 6 days and removal of the balloon at 34 weeks plus 0 day to 34 weeks plus 6 days.
干预措施: Baltaccidbpe100 Delivery Catheter (Device)
Prenatal Intervention (FETO)
Patients will undergo fetoscopic endoluminal tracheal occlusion and ideally prenatal reversal of the occlusion followed by standardized postnatal care as in the expectant . In this study FETO (where GoldBal2 detachable balloon and Baltaccidbpe100 Delivery Catheter are used) is to be done between 30 weeks plus 0 day and 31 weeks plus 6 days and removal of the balloon at 34 weeks plus 0 day to 34 weeks plus 6 days.
干预措施: Standardized postnatal care (Other)
结局指标
主要结局
Proportion of Neonate Survival at Discharge From Hospital
时间窗: At hospital discharge, an average of 1.5 months
The null hypothesis to be tested is that there is no difference in survival between fetuses managed expectantly during pregnancy versus those undergoing antenatal therapy (FETO).
Participants Requiring Supplemental Oxygen
时间窗: At 6 months of age
The number of survivors requiring supplemental oxygen at 6 months of age
次要结局
- Occurrence of Severe Pulmonary Hypertension(During the first 4 weeks of life (neonatal period).)
- ECMO (Extracorporeal Membrane Oxygenation) Support(Neonatal period (during the first 4 weeks of life))
- Grade of Oxygen Dependency(at 6 months of age)
- CDH Defect Size(Measured in neonate at delivery by MRI and/or ultrasound)
- Number of Days in the NICU(At the time of discharge from the NICU, an average of 1.5 months)
- Ventilatory Support(During the first 4 weeks of life (neonatal period))
- Number of Subjects With Periventricular Leukomalacia (PVL)(During first 2 months of life)
- Neonatal Sepsis(During the first 4 weeks of life (neonatal period))
- Intraventricular Hemorrhage(During first month of life)
- Retinopathy of Prematurity(At the time of discharge from the NICU, an average of 1.5 months)
- Days to Full Enteral Feeding(At hospital discharge, an average of 1.5 months)
- Gastroesophageal Reflux(At the time of discharge from the NICU, an average of 1.5 months)
- CDH (Congenital Diaphragmatic Hernia) Surgery Repair(From the time of birth until discharge from the NICU)
- Use of Patch in CDH Repair(At the time of the surgical repair postnatally, up to 3 days postnatal)
- Survival(At 24 months of age)
研究者
Michael A Belfort
Principal Investigator
Baylor College of Medicine