Clinical trial NCT03431792: FETO With Long Tail Balloon for a Treatment of Severe CDH
Official title: The Intrauterine Fetoscopic Tracheal Occlusion (FETO) With Long Tail Balloon for a Treatment of Severe Congenital Diaphragmatic Hernia (CDH)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Severe Congenital Diaphragmatic Hernia
Keywords: CDH, FETO, fetal surgery, long tail FETO
Lead sponsor: Martin-Luther-Universität Halle-Wittenberg
Sponsor class: OTHER
First posted: 2018-02-13
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 48
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Treatment of fetuses with severe CDH with an observed / expected total fetal lung volume ratio (o/e TFLV) ratio \< 25% or with o/e TFLV ratio \< 35% combined with herniation of the liver in thorax using the intrauterine fetoscopic tracheal occlusion (FETO) with the long tail latex balloon of 2.5 ml.
Primary purpose: TREATMENT

Brief summary: Congenital diaphragmatic hernia (CDH) has an incidence of 1:2200 to 1:4000 newborns. The survival rate depends on the extent of the lung hypoplasia and pulmonary hypertension. In case of an observed / expected total fetal lung volume ratio (o/e TFLV) ratio of 25% or lower and herniation of the liver in thorax, the postnatal survival is estimated to be 10-25% or lower. The aim of fetoscopic tracheal balloon occlusion is to positively influence the lung growth in CDH fetuses avoiding the development of lung hypoplasia.

Some complications after sucsessfull FETO before delivery occur because of technical difficulties during the extraction of the balloon from the trachea, leading to asphyxia, worse outcome or neonatal demise. Jani et al. published 10 neonatal deaths from 210 FETO directly related to difficulties with the removal of the intratracheal balloon. The risk of emergent balloon removal was published to be very high (39%-56%).

Our new technique exploits the fetal ability to removal the intratracheal balloon which has been implanted for the treatment of severe CDH before the delivery, avoiding many risks associated with balloon extraction and a second fetoscopy.

The study will be performed on 20 fetuses with severe CDH. Before the FETO the total fetal lung volume ratio (o/e TFLV) will be measured by fetal MRI (magnetic . Only CDH fetuses with 24-32 weeks' gestation with o/e TFLV \< 25% or the fetuses with o/e TFLV \< 35% and liver herniation will be operated Second fetal MRI should be performed in one week after the FETO. The balloon will be extracted by the fetus itself before the delivery, after puncture with 22 gauge needle under ultrasound guiding, during second fetoscopy or using the EXIT (ex utero intrapartum Treatment). Neonatal follow up 12 months.

Detailed description: Congenital diaphragmatic hernia (CDH) has an incidence of 1:2200 to 1:4000 newborns, depending on whether stillbirths are included or not. 40 % of all CDH cases show associated malformations and chromosomal abnormalities and/or syndromes take place in 10-20%. The survival rate depends on the extent of the lung hypoplasia and pulmonary hypertension. Liver herniation into the thorax, is also a negative predictor of fetal survival. In case of an observed / expected total fetal lung volume ratio (o/e TFLV) ratio of 25% or lower and herniation of the liver in thorax, the postnatal survival is estimated to be 10-25% or lower. The aim of fetoscopic tracheal balloon occlusion is to positively influence the lung growth in CDH fetuses avoiding the development of lung hypoplasia.

A common complication of fetal surgery is the preterm premature rupture of membranes (PPROM) leading to preterm delivery. The next problem occurs because of technical difficulties during the extraction of the balloon from the trachea, leading to asphyxia, worse outcome or neonatal demise. Jani et al. published 10 neonatal deaths from 210 FETO directly related to difficulties with the removal of the intratracheal balloon. The risk of emergent balloon removal was published to be very high (39%-56%).

Our new long tail balloon exploits the fetal ability to removal the intratracheal balloon which has been implanted for the treatment of severe CDH before the delivery, avoiding many risks associated with balloon extraction and a second fetoscopy.

The study will be performed on 20 fetuses with severe CDH with total fetal lung volume ratio (o/e TFLV) \< 25% or with o/e TFLV \< 35% combined with liver herniation into the thorax. The lung volume will be estimated by fetal MRI. The selected fetuses with severe CDH at 24-32 weeks' gestation will be operated.

Before the Long tail FETO the 0.1 mg/kg Pancuronium, 1 µg/kg Fentanyl® and 0.01 mg/kg atropine will be applicated i.m. to the CDH fetus using 22 gauge needle under ultrasound control. The monofilament 5-0 polypropylene suture of 7 cm will be fixed to the balloon (Goldbal 5, 2,5 ml, BALT Extrusion, Montmorency, France) and the FETO will be performed. The fetoscope (Karl Storz, Tuttlingen, Germany) with a diameter of 1.3 mm will be percutaneously inserted through a sheath into the uterus and then into the fetal trachea. The fetoscope will be removed and the long tail balloon will be inserted under 4-D ultrasound guidance.The position of the balloon and suture will be controlled by fetoscopy and sonography.

Second fetal MRI should be performed in one week after the FETO. The balloon must be extracted before the delivery.

Possibilities of the Long tail extraction:

1. The fetus is able to extract the balloon from the trachea after FETO, by pulling the balloons' long tail, at the end of pregnancy;
2. by fetus itself after balloon puncture with 22 gauge needle under ultrasound guiding;
3. during second fetoscopy;
4. or using the EXIT procedure.

The CDH will be closed with / or without a patch. The follow up examinations will be performed at 6 and 12 months of age the baby.

Eligibility criteria: Inclusion Criteria:

* maternal age of 18-48 years
* severe CDH with MRI measured observed/expected total fetal lung volume (o/e TFLV) \< 25% or \< 35% in combination with a liver herniation into the thorax.

Exclusion Criteria:

* fetuses with other letal morphological abnormalities
* fetuses with chromosomal abnormalities
* severe maternal illneses

Primary outcomes:
measure: neonatal survival
timeFrame: 1 year
Secondary outcomes:
measure: pulmonary hypoplasia
timeFrame: 1 year
measure: Diaphragmatic Hernia operation
timeFrame: 1 year
measure: necrotizing enterocolitis
timeFrame: 1 year
measure: neurodevelopmental impairment
timeFrame: 1 year
measure: APGAR
timeFrame: during the first 10 min after the delivery
measure: umbilical artery pH
timeFrame: during 10 min after the delivery
measure: weight
timeFrame: 24hour
measure: length
timeFrame: 24hour
measure: Duration of O2-Ventilation (day)
timeFrame: 1 year
Other outcomes:
Locations:
city: Halle
country: Germany
facility: Center of Fetal Surgery, Clinic of Obstetrics and Perinatal Medicine, Martin-Luther-University Halle-Wittenberg
Study officials:
affiliation: Germany, Center of Fetal Surgery, Martin-Luther University Halle-Wittenberg
name: Michael Tchirikov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tchirikov M, Gatopoulos G, Strohner M, Puhl A, Steetskamp J. Two new approaches in intrauterine tracheal occlusion using an ultrathin fetoscope. Laryngoscope. 2010 Feb;120(2):394-8. doi: 10.1002/lary.20687.
citation: Tchirikov M. Successful tracheal occlusion using ultrathin fetoscopic equipment combined with real-time three-dimensional ultrasound. Eur Surg Res. 2009;43(2):204-7. doi: 10.1159/000224146. Epub 2009 Jun 10.
citation: Jani JC, Nicolaides KH, Gratacos E, Valencia CM, Done E, Martinez JM, Gucciardo L, Cruz R, Deprest JA. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009 Sep;34(3):304-10. doi: 10.1002/uog.6450.