Fetal Surgery for Moderate Left Sided Congenital Diaphragmatic Hernia. (TOTAL moderate)

November 30, 2020 updated by: Jan Deprest, University Hospital, Gasthuisberg

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.

Isolated Congenital Diaphragmatic Hernia (CDH) can be diagnosed in the prenatal period, and remains associated with a 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 55%.

This trial will test whether temporary fetoscopic tracheal occlusion rather than expectant management during pregnancy, both followed by standardized postnatal management increases survival or decrease oxygen dependency at 6 months of age. The balloon will be placed between 30 and 31+6 weeks, and will be removed between 34 and 34+6 weeks.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

196

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • Brisbane, Queensland, Australia, 4101
        • Mater Mother's Hospital
  • Belgium
      • Leuven, Belgium, 3000
        • University Hospitals Leuven
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital
  • France
      • Clamart, France, 92141
        • Hôpital Antoine Béclère
      • Paris, France, 75743
        • Hôpital Necker - Enfants Malades
  • Germany
      • Bonn, Germany, 53105
        • University Hospital of Bonn
  • Italy
      • Milan, Italy, 20122
        • Ospedale Maggiore Policlinico
      • Rome, Italy, 00123
        • Ospedale Pediatrico Bambino Gesù
  • Poland
      • Warsaw, Poland
        • 1st Department of Obstetrics and Gynecology, Medical University of Warsaw
  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08028
        • Hospital Clinic Barcelona
  • United Kingdom
      • London, United Kingdom, SE5 9RS
        • King's College Hospital
  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas Health Science Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Texas Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: FETO
prenatal FETO at 30-31+6 weeks and removal at 34-34+6 wks, followed by standardized postnatal care
Procedure: Fetoscopic Endoluminal Tracheal Occlusion
prenatal balloon placement at 30-31+6 weeks and removal at 34-34+6 wks
No Intervention: Expectant management
expectant management during pregnancy followed by standardized neonatal care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Survival at discharge
Time Frame: at the time of discharge from NICU, approximately 2 months
at the time of discharge from NICU, approximately 2 months
Supplemental oxygen at 6 months of age
Time Frame: at 6 months of age
at 6 months of age

Secondary Outcome Measures

Outcome Measure
Time Frame
Grading of oxygen dependency
Time Frame: between 28 and 56 days of life if born >32 weeks; at 36 weeks postmenstrual age if born <32 weeks
between 28 and 56 days of life if born >32 weeks; at 36 weeks postmenstrual age if born <32 weeks
Pulmonary hypertension
Time Frame: during NICU admission
during NICU admission
Use of extracorporeal membrane oxygenation
Time Frame: during NICU admission
during NICU admission
Change in O/E LHR after FETO
Time Frame: prior to unplug
prior to unplug
NICU days
Time Frame: during NICU admission
during NICU admission
days of ventilatory support
Time Frame: during NICU admission
during NICU admission
Periventricular leucomalacia
Time Frame: during NICU admission
during NICU admission
Neonatal sepsis
Time Frame: during NICU admission
during NICU admission
Intraventricular hemorrhage
Time Frame: during NICU admission
during NICU admission
Retinopathy of prematurity
Time Frame: during NICU admission
during NICU admission
Days until full enteral feeding
Time Frame: during NICU admission
during NICU admission
Gastroesophageal reflux
Time Frame: during NICU admission
during NICU admission
Day of postnatal surgery
Time Frame: during NICU admission
during NICU admission
Use of patch
Time Frame: at the time of postnatal surgery
at the time of postnatal surgery
Defect size
Time Frame: at the time of postnatal surgery
at the time of postnatal surgery
Number of days alive in case of postnatal death
Time Frame: during NICU admission
during NICU admission

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Gasthuisberg

Collaborators

The University of Texas Health Science Center, Houston
Baylor College of Medicine
Hospital Clinic of Barcelona
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
University Hospital, Bonn
Mount Sinai Hospital, Canada
Medical University of Warsaw
Hôpital Necker-Enfants Malades
Hopital Antoine Beclere
King's College Hospital NHS Trust (UK)
Mater Mothers' Hospital
Ospedale Pediatrico Bambino Gesù, Rome (IT)

Investigators

  • Study Chair: Jan A Deprest, MD PhD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (Actual)

March 1, 2020

Study Completion (Actual)

March 1, 2020

Study Registration Dates

First Submitted

September 30, 2008

First Submitted That Met QC Criteria

September 30, 2008

First Posted (Estimate)

October 1, 2008

Study Record Updates

Last Update Posted (Actual)

December 3, 2020

Last Update Submitted That Met QC Criteria

November 30, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B32220084540
  • 2008-4634 (Other Identifier: Hospital Clinic Barcelona)
  • ML4999- B32220084540 (Other Identifier: University Hospitals Leuven)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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