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Randomized Controlled Trial of Fetoscopic Endoluminal Tracheal Occlusion With a Balloon Versus Expectant Management During Pregnancy in Fetuses With Left Sided Congenital Diaphragmatic Hernia and Moderate Pulmonary Hypoplasia. (TOTAL moderate)

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ClinicalTrials.gov Identifier: NCT00763737
Recruitment Status : Recruiting
First Posted : October 1, 2008
Last Update Posted : December 15, 2016
Information provided by (Responsible Party):

Study Description
Brief Summary:

Isolated Congenital Diaphragmatic Hernia (CDH) can be diagnosed in the prenatal period, and remains associated with an 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 60% or lower and the rate of broncho-pulmonary dysplasia in survivors is 33% or higher.

This trial will test whether temporary fetoscopic tracheal occlusion rather than expectant management during pregnancy, both followed by standardized postnatal management, decreases the occurrence of bronchopulmonary dysplasia or increases survival. The balloon will be placed between 30 and 32+6 weeks, and will be removed between 34 and 34+6 weeks.

Condition or disease Intervention/treatment
Congenital Diaphragmatic Hernia Fetal Surgery Pulmonary Hypoplasia Procedure: Fetoscopic Endoluminal Tracheal Occlusion

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 196 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Study Start Date : August 2010
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : December 2018

Arms and Interventions

Arm Intervention/treatment
Experimental: 1
prenatal FETO at 30-32+6 weeks and removal at 34-34+6 wks, followed by standardized postnatal care
Procedure: Fetoscopic Endoluminal Tracheal Occlusion
prenatal balloon placement at 30-32+6 weeks and removal at 34-34+6 wks
No Intervention: 2
expectant management during pregnancy followed by standardized neonatal care

Outcome Measures

Primary Outcome Measures :
  1. Survival at discharge [ Time Frame: at discharge from hospital ]

Secondary Outcome Measures :
  1. occurrence of bronchopulmonary dysplasia [ Time Frame: 28 days of life ]
  2. Oxygen dependency at discharge [ Time Frame: at discharge from hospital ]
  3. Survival without oxygen dependency [ Time Frame: 6 months of life ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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 32 wks plus 5 d (so that occlusion is done at the latest on 32 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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00763737

Contact: Jan A Deprest, MD PhD +3216344215 Jan.Deprest@uzleuven.be
Contact: Leen Mortier +32 16 34 42 15 leen.mortier@uzleuven.be

United States, Texas
Baylor College of Medicine/Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Michael Belfort, MD, PhD    832-826-7375    belfort@bcm.edu   
Australia, Queensland
Mater Mother's Hospital Recruiting
Brisbane, Queensland, Australia, 4101
Contact: Glenn Gardener, MD, PhD       glenn.gardener@mater.org.au   
University Hospitals Leuven Recruiting
Leuven, Belgium, 3000
Contact: Jan A Deprest, MD PhD    +3216344215    Jan.Deprest@uzleuven.be   
Principal Investigator: Jan A Deprest, MD PhD         
Canada, Ontario
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G 1X5
Contact: Greg Ryan, MD, PhD       gryan@mtsinai.on.ca   
Hôpital Antoine Béclère Recruiting
Clamart, France, 92141
Contact: Alexandra Benachi, MD, PhD       alexandra.benachi@abc.aphp.fr   
Hôpital Necker - Enfants Malades Recruiting
Paris, France, 75743
Contact: Yves Ville, MD, PhD       yves.ville@nck.aphp.fr   
University Hospital of Bonn Recruiting
Bonn, Germany, 53105
Contact: Christoph Berg, MD, PhD       christoph.berg@ukb.uni-bonn.de   
Ospedale Maggiore Policlinico Recruiting
Milan, Italy, 20122
Contact: Nicola Persico, MD, PhD       nicola.persico@gmail.com   
Ospedale Pediatrico Bambino Gesù Recruiting
Rome, Italy, 00123
Contact: Pietro Bagolan, MD, PhD       pietro.bagolan@opbg.net   
Hospital Clinic Barcelona Recruiting
Barcelona, Catalunya, Spain, 08028
Contact: Eduardo Gratacos, MD PhD    +34 (93) 227 99 46    egratacos@clinic.ub.es   
Principal Investigator: Eduardo Gratacos, MD PhD         
United Kingdom
King's College Hospital Recruiting
London, United Kingdom, SE5 9RS
Contact: Kypros Nicolaides, MD, PhD       kypros@fetalmedicine.com   
Sponsors and Collaborators
University Hospital, Gasthuisberg
King's College Hospital NHS Trust (UK)
Hospital Clinic of Barcelona (ES)
Hôpital Antoine Béclère, Clamart (FR)
Hôpital Necker - Enfants Malades, Paris (FR)
University Hospital, Bonn
Mater Mother's Hospital, Brisbane (AUS)
Ospedale Maggiore Policlinico, Milan (IT)
Ospedale Pediatrico Bambino Gesù, Rome (IT)
Mount Sinai Hospital, Toronto (CAN)
Baylor College of Medicine/Texas Children's Hospital (US)
Study Chair: Jan A Deprest, MD PhD Universitaire Ziekenhuizen Leuven
More Information

Additional Information:

Responsible Party: Jan Deprest, Jan Deprest, MD PhD, Professor in Obstetrics and Gynaecology, Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT00763737     History of Changes
Other Study ID Numbers: B32220084540
2008-4634 ( Other Identifier: Hospital Clinic Barcelona )
ML4999- B32220084540 ( Other Identifier: University Hospitals Leuven )
First Posted: October 1, 2008    Key Record Dates
Last Update Posted: December 15, 2016
Last Verified: December 2016

Keywords provided by Jan Deprest, Universitaire Ziekenhuizen Leuven:
congenital diaphragmatic hernia
fetal surgery
pulmonary hypoplasia
observed/expected lung to head ratio
liver position
fetoscopic endoluminal tracheal occlusion
standardized neonatal care

Additional relevant MeSH terms:
Hernia, Diaphragmatic
Hernias, Diaphragmatic, Congenital
Pathological Conditions, Anatomical
Congenital Abnormalities