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
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 196
- 试验地点
- 25
- 主要终点
- Survival at discharge
研究概览
简要总结
Isolated Congenital Diaphragmatic Hernia (CDH) can be diagnosed in the prenatal period, and remains associated with a 30 % chance of perinatal death and morbidity mainly because of pulmonary hypoplasia and pulmonary hypertension. In addition, in the survivors there is a high rate of morbidity with evidence of bronchopulmonary dysplasia in more than 70% of cases. The risk for these can be predicted prenatally by the ultrasonographic measurement of the observed/expected lung area to head circumference ratio (O/E LHR) which is a measure of pulmonary hypoplasia. Also position of the liver is predictive of outcome.
The proposing consortium has developed a prenatal therapeutic approach, which consists of percutaneous fetoscopic endoluminal tracheal occlusion (FETO) with subsequent removal of the balloon. Both procedures are performed percutaneously, there is now experience with more than 150 cases and it has been shown to be safe for the mother. We have witnessed an improvement of survival in fetuses with a predicted chance of survival of less than 30% (referred to as fetuses with severe pulmonary hypoplasia; O/E LHR <25% and liver herniation) to 55% on average. Also there is an apparent reduction in morbidity with the rate of bronchopulmonary dysplasia decreasing from the estimated rate of more than 70% to less than 40% in the same severity group.
Further we have shown that results of FETO are predicted by LHR measurement prior to the procedure, so that better results can be expected in fetuses with larger lung size. Therefore we now aim to offer FETO to fetuses with moderate CDH (=O/E LHR 25-34.9%, irrespective of the liver position as well as O/E LHR 35-44.9% with intrathoracic herniation of the liver). When managed expectantly the estimated rate of postnatal survival is 55%.
This trial will test whether temporary fetoscopic tracheal occlusion rather than expectant management during pregnancy, both followed by standardized postnatal management increases survival or decrease oxygen dependency at 6 months of age. The balloon will be placed between 30 and 31+6 weeks, and will be removed between 34 and 34+6 weeks.
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 —（Adult, Older 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
- •Anatomically and chromosomally normal fetus
- •Left sided diaphragmatic hernia
- •Gestation at randomization prior to 31 wks plus 5 d (so that occlusion is done at the latest on 31 wks plus 6 d)
- •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
- •Acceptance of randomization and the consequences for the further management during pregnancy and thereafter.
- •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".
- •Provide written consent to participate in this RCT
排除标准
- •Maternal contraindication to fetoscopic surgery or severe medical condition in pregnancy that make fetal intervention risk full
- •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 labour, cervix shortened (<15 mm at randomization) or uterine anomaly strongly predisposing to preterm labour, 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
- •Patient refusing randomization or to comply with return to FETO center during the time period the airways are occluded or for elective removal of the balloon
结局指标
主要结局
Survival at discharge
时间窗: at the time of discharge from NICU, approximately 2 months
Supplemental oxygen at 6 months of age
时间窗: at 6 months of age
次要结局
- NICU days(during NICU admission)
- Neonatal sepsis(during NICU admission)
- Days until full enteral feeding(during NICU admission)
- Day of postnatal surgery(during NICU admission)
- days of ventilatory support(during NICU admission)
- Intraventricular hemorrhage(during NICU admission)
- Retinopathy of prematurity(during NICU admission)
- Pulmonary hypertension(during NICU admission)
- Use of extracorporeal membrane oxygenation(during NICU admission)
- Number of days alive in case of postnatal death(during NICU admission)
- Grading of oxygen dependency(between 28 and 56 days of life if born >32 weeks; at 36 weeks postmenstrual age if born <32 weeks)
- Use of patch(at the time of postnatal surgery)
- Periventricular leucomalacia(during NICU admission)
- Gastroesophageal reflux(during NICU admission)
- Change in O/E LHR after FETO(prior to unplug)
- Defect size(at the time of postnatal surgery)
研究者
Jan Deprest
Jan Deprest, MD PhD, Professor in Obstetrics and Gynaecology
Universitaire Ziekenhuizen KU Leuven