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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 : January 9, 2019
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, Bonn
Mater Mother's Hospital, Brisbane (AUS)
Ospedale Maggiore Policlinico, Milan (IT)
Ospedale Pediatrico Bambino Gesù, Rome (IT)
Mount Sinai Hospital, Canada
Baylor College of Medicine
University of Texas Health Science Center at Houston, TX (US)
Information provided by (Responsible Party):
Jan Deprest, Universitaire Ziekenhuizen Leuven

Tracking Information
First Submitted Date  ICMJE September 30, 2008
First Posted Date  ICMJE October 1, 2008
Last Update Posted Date January 9, 2019
Study Start Date  ICMJE August 2010
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 14, 2016)
Survival at discharge [ Time Frame: at discharge from hospital ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 30, 2008)
Occurrence of broncho-pulmonary dysplasia at 28 days of life [ Time Frame: 28 days of life ]
Change History Complete list of historical versions of study NCT00763737 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2016)
  • occurrence of bronchopulmonary dysplasia [ Time Frame: 28 days of life ]
  • Oxygen dependency at discharge [ Time Frame: at discharge from hospital ]
  • Survival without oxygen dependency [ Time Frame: 6 months of life ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2008)
  • Survival at discharge [ Time Frame: at discharge from hospital ]
  • Survival free of bronchopulmonary dysplasia at 28 days of life [ Time Frame: 28 days of life ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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.
Official Title  ICMJE 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.
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 31+6 weeks, and will be removed between 34 and 34+6 weeks.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Congenital Diaphragmatic Hernia
  • Fetal Surgery
  • Pulmonary Hypoplasia
Intervention  ICMJE Procedure: Fetoscopic Endoluminal Tracheal Occlusion
prenatal balloon placement at 30-31+6 weeks and removal at 34-34+6 wks
Study Arms  ICMJE
  • Experimental: 1
    prenatal FETO at 30-31+6 weeks and removal at 34-34+6 wks, followed by standardized postnatal care
    Intervention: Procedure: Fetoscopic Endoluminal Tracheal Occlusion
  • No Intervention: 2
    expectant management during pregnancy followed by standardized neonatal care
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 3, 2016)
196
Original Estimated Enrollment  ICMJE
 (submitted: September 30, 2008)
152
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 31 wks plus 5 d (so that occlusion is done at the latest on 31 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jan A Deprest, MD PhD +3216344215 Jan.Deprest@uzleuven.be
Contact: Leen Mortier +32 16 34 42 15 leen.mortier@uzleuven.be
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00763737
Other Study ID Numbers  ICMJE B32220084540
2008-4634 ( Other Identifier: Hospital Clinic Barcelona )
ML4999- B32220084540 ( Other Identifier: University Hospitals Leuven )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jan Deprest, Universitaire Ziekenhuizen Leuven
Study Sponsor  ICMJE University Hospital, Gasthuisberg
Collaborators  ICMJE
  • 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, Canada
  • Baylor College of Medicine
  • University of Texas Health Science Center at Houston, TX (US)
Investigators  ICMJE
Study Chair: Jan A Deprest, MD PhD Universitaire Ziekenhuizen Leuven
PRS Account University Hospital, Gasthuisberg
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP