Fetal Surgery for Moderate Left Sided Congenital Diaphragmatic Hernia.

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Congenital Diaphragmatic Hernia, Fetal Surgery, Pulmonary Hypoplasia

Intervention / Treatment
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* Procedure: Fetoscopic Endoluminal Tracheal Occlusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FETO<br>prenatal FETO at 30-31+6 weeks and removal at 34-34+6 wks, followed by standardized postnatal care | Procedure: Fetoscopic Endoluminal Tracheal Occlusion<br>* prenatal balloon placement at 30-31+6 weeks and removal at 34-34+6 wks<br>|
| No Intervention: Expectant management<br>expectant management during pregnancy followed by standardized neonatal care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at discharge |  | at the time of discharge from NICU, approximately 2 months | 
| Supplemental oxygen at 6 months of age |  | at 6 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grading of oxygen dependency |  | between 28 and 56 days of life if born >32 weeks; at 36 weeks postmenstrual age if born <32 weeks | 
| Pulmonary hypertension |  | during NICU admission | 
| Use of extracorporeal membrane oxygenation |  | during NICU admission | 
| Change in O/E LHR after FETO |  | prior to unplug | 
| NICU days |  | during NICU admission | 
| days of ventilatory support |  | during NICU admission | 
| Periventricular leucomalacia |  | during NICU admission | 
| Neonatal sepsis |  | during NICU admission | 
| Intraventricular hemorrhage |  | during NICU admission | 
| Retinopathy of prematurity |  | during NICU admission | 
| Days until full enteral feeding |  | during NICU admission | 
| Gastroesophageal reflux |  | during NICU admission | 
| Day of postnatal surgery |  | during NICU admission | 
| Use of patch |  | at the time of postnatal surgery | 
| Defect size |  | at the time of postnatal surgery | 
| Number of days alive in case of postnatal death |  | during NICU admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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congenital diaphragmatic hernia, fetal surgery, pulmonary hypoplasia, observed/expected lung to head ratio, liver position, feto, fetoscopic endoluminal tracheal occlusion, standardized neonatal care