Tracheal Occlusion To Accelerate Lung Growth (TOTAL) Trial for Severe Pulmonary Hypoplasia

Study Overview
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Brief Summary
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This trial investigates whether prenatal intervention improves survival rate of fetuses with isolated congenital diaphragmatic hernia and severe pulmonary hypoplasia, as compared to expectant management during pregnancy, both followed by standardized postnatal care.

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 Diaphragma Hernia and Severe Pulmonary Hypoplasia.

Conditions
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Congenital Diseases, Diaphragmatic Hernia, Pulmonary Hypoplasia

Intervention / Treatment
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* Procedure: fetal endoluminal tracheal occlusion
* Other: watchful waiting during pregnancy


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 29 wks plus 5 d (so that occlusion is done at the latest on 29 wks plus 6 d) Estimated to have severe pulmonary hypoplasia, defined prenatally as: O/E LHR <25 %, irrespective of the liver position 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
Maximum Age: 50 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 |
| --- | --- |
| Placebo Comparator: expectant management during pregnancy<br>watchful waiting during pregnancy | Other: watchful waiting during pregnancy<br>* pregnancy surveillance for fetal wellbeing, development of polyhydramnios and cervical shortening<br>|
| Experimental: fetal endoluminal tracheal occlusion<br>fetoscopic balloon occlusion at 27 to 29+6 weeks of gestation | Procedure: fetal endoluminal tracheal occlusion<br>* percutaneous fetoscopy, positioning of endoluminal balloon at 27-30 weeks and whenever possible elective removal at 34 weeks<br>* Other names: Balt Goldbal 2 balloon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at discharge from neonatal intensive care unit | The baby can be discharged either alive (and then it qualifies as surviving at discharge) or dead. Not discharged babies have not reached the primary endpoint. | at discharge from neonatal intensive care unit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prenatal increase in lung volume after FETO | volume of lung after occlusion | prior to balloon removal | 
| grading of oxygen dependency |  | born >32 wks: between 28-56d of life; born <32wks: 36wks postmenstrual age | 
| occurrence of pulmonary hypertension | determined by cardiac ultrasound | within first weeks of life | 
| number of days in Neonatal Intensive Care Unit (NICU) | As long as the baby is in the hospital, it is hospitalized either in NICU or in another, less intensive care unit. The number of days in NICU is an outcome variable, expressed in days. | within hospital stay | 
| number of days of ventilatory support |  | within NICU stay | 
| presence of periventricular leucomalacia |  | 2 months of life | 
| presence of neonatal sepsis, intraventricular haemorrhage, retinopathy grade III or higher |  | within hospital stay | 
| number of days till full enteral feeding |  | within first 2 years of life | 
| presence of gastro-esophagal reflux |  | at discharge | 
| day of surgery |  | within hospital stay | 
| requirement for use of patch for repair |  | at the time of postnatal surgery | 
| bronchopulmonary dysplasia | defined as oxygen need for at least 28 days | with the first 8 weeks | 
| Need for Extracorporeal membrane oxygenation |  | during NICU admission | 
| 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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Isolated Congenital Diaphragmatic Hernia, Fetal Surgery, Pulmonary Hypoplasia