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OpenTrials
Completed

NCT Number: NCT00763737

Fetal Surgery for Moderate Left Sided Congenital Diaphragmatic Hernia.

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.

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Key information

Conditions

Congenital Diaphragmatic Hernia Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Fetal Surgery Hernia Hernia, Diaphragmatic Hernias, Diaphragmatic, Congenital Internal Hernia Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Pulmonary Hypoplasia

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Mater Mother's Hospital, Brisbane, Queensland, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Fetoscopic Endoluminal Tracheal Occlusion

Procedure

prenatal balloon placement at 30-31+6 weeks and removal at 34-34+6 wks

Primary outcomes

  1. Survival at discharge

    Time frame: at the time of discharge from NICU, approximately 2 months

  2. Supplemental oxygen at 6 months of age

    Time frame: at 6 months of age

Secondary outcomes

  1. 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

  2. Pulmonary hypertension

    Time frame: during NICU admission

  3. Use of extracorporeal membrane oxygenation

    Time frame: during NICU admission

  4. Change in O/E LHR after FETO

    Time frame: prior to unplug

  5. NICU days

    Time frame: during NICU admission

  6. days of ventilatory support

    Time frame: during NICU admission

  7. Periventricular leucomalacia

    Time frame: during NICU admission

  8. Neonatal sepsis

    Time frame: during NICU admission

  9. Intraventricular hemorrhage

    Time frame: during NICU admission

  10. Retinopathy of prematurity

    Time frame: during NICU admission

  11. Days until full enteral feeding

    Time frame: during NICU admission

  12. Gastroesophageal reflux

    Time frame: during NICU admission

  13. Day of postnatal surgery

    Time frame: during NICU admission

  14. Use of patch

    Time frame: at the time of postnatal surgery

  15. Defect size

    Time frame: at the time of postnatal surgery

  16. Number of days alive in case of postnatal death

    Time frame: during NICU admission

Sponsors and collaborators

Lead sponsor

University Hospital, Gasthuisberg

Other

Collaborators

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

Registry information

Official study 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.

Acronym: TOTAL moderate

Important dates

Study start
2010
Primary completion
2020
Study completion
2020
First posted
Oct 1, 2008
Registry last updated
Dec 3, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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