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Randomized Control 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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by University Hospital, Gasthuisberg
Sponsor:
Collaborators:
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 of Bonn, (DE)
Mater Mother's Hospital, Brisbane (AUS)
Ospedale Maggiore Policlinico, Milan (IT)
Ospedale Pediatrico Bambino Gesù, Rome (IT)
Mount Sinai Hospital, Toronto (CAN)
Information provided by (Responsible Party):
Jan Deprest, Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier:
NCT00763737
First received: September 30, 2008
Last updated: November 28, 2016
Last verified: November 2016
  Purpose

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 35+6 weeks.


Condition Intervention
Congenital Diaphragmatic Hernia
Fetal Surgery
Pulmonary Hypoplasia
Procedure: Fetoscopic Endoluminal Tracheal Occlusion

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by University Hospital, Gasthuisberg:

Primary Outcome Measures:
  • Oxygen dependency [ Time Frame: 6 months of life ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival at discharge [ Time Frame: at discharge from hospital ] [ Designated as safety issue: No ]
  • occurrence of bronchopulmonary dysplasia [ Time Frame: 28 days of life ] [ Designated as safety issue: No ]
  • Oxygen dependency at discharge [ Time Frame: at discharge from hospital ] [ Designated as safety issue: No ]

Estimated Enrollment: 152
Study Start Date: August 2010
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
prenatal FETO at 30-32+6 weeks and removal at 34-35 wks, followed by standardized postnatal care
Procedure: Fetoscopic Endoluminal Tracheal Occlusion
prenatal balloon placement at 30-32+6 weeks and removal at 34-35 wks
No Intervention: 2
expectant management during pregnancy followed by standardized neonatal care

  Eligibility

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00763737

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

Locations
United States, Texas
Texas Medical Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Michael Belfort, MD, PhD       belfort@bcm.edu   
Australia, Queensland
Mater Mother's Hospital Recruiting
Brisbane, Queensland, Australia, 4101
Contact: Glenn Gardener, MD, PhD       glenn.gardener@mater.org.au   
Belgium
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   
France
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   
Germany
University Hospital of Bonn Recruiting
Bonn, Germany, 53105
Contact: Christoph Berg, MD, PhD       christoph.berg@ukb.uni-bonn.de   
Italy
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   
Spain
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 of Bonn, (DE)
Mater Mother's Hospital, Brisbane (AUS)
Ospedale Maggiore Policlinico, Milan (IT)
Ospedale Pediatrico Bambino Gesù, Rome (IT)
Mount Sinai Hospital, Toronto (CAN)
Investigators
Study Chair: Jan A Deprest, MD PhD Universitaire Ziekenhuizen Leuven
  More Information

Additional Information:
Publications:

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  ML4999- B32220084540 
Study First Received: September 30, 2008
Last Updated: November 28, 2016
Health Authority: European Commission (6th Framework programme): Belgium
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by University Hospital, Gasthuisberg:
congenital diaphragmatic hernia
fetal surgery
pulmonary hypoplasia
observed/expected lung to head ratio
liver position
feto
fetoscopic endoluminal tracheal occlusion
standardized neonatal care

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

ClinicalTrials.gov processed this record on December 05, 2016