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)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2008 by University Hospital, Gasthuisberg.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
King's College Hospital NHS Trust
Hospital Clinic of Barcelona
Information provided by:
University Hospital, Gasthuisberg
ClinicalTrials.gov Identifier:
NCT00763737
First received: September 30, 2008
Last updated: January 11, 2010
Last verified: September 2008
  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
Procedure: expectant management during pregnancy

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:
  • surviving without broncho-pulmonary dysplasia [ Time Frame: 28 days 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 ]

Estimated Enrollment: 152
Study Start Date: September 2008
Estimated Study Completion Date: September 2012
Estimated Primary Completion Date: September 2012 (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
Procedure: expectant management during pregnancy
observation

  Eligibility

Ages Eligible for Study:   18 Years and older
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: Tim Van Mieghem, MD +3216340829 Tim.VanMieghem@uzleuven.be

Locations
Belgium
University Hospitals Leuven Recruiting
Leuven, Belgium, 3000
Contact: Jan A Deprest, MD PhD    +3216344215    Jan.Deprest@uzleuven.be   
Contact: Tim Van Mieghem, MD    +3216340829    Tim.VanMieghem@uzleuven.be   
Principal Investigator: Jan A Deprest, MD PhD         
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         
Sponsors and Collaborators
University Hospital, Gasthuisberg
King's College Hospital NHS Trust
Hospital Clinic of Barcelona
Investigators
Study Chair: Jan A Deprest, MD PhD Universitaire Ziekenhuizen Leuven
  More Information

Additional Information:
Publications:

Responsible Party: Jan Deprest, MD PhD, Professor in Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium
ClinicalTrials.gov Identifier: NCT00763737     History of Changes
Other Study ID Numbers: B32220084540, 2008-4634, ML4999- B32220084540
Study First Received: September 30, 2008
Last Updated: January 11, 2010
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
Hernia, Hiatal
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on July 22, 2014