Fetal Surgery for Moderate Left Sided Congenital Diaphragmatic Hernia.
NCT ID: NCT00763737
Last Updated: 2020-12-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
196 participants
INTERVENTIONAL
2010-08-31
2020-03-31
Brief Summary
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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.
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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FETO
prenatal FETO at 30-31+6 weeks and removal at 34-34+6 wks, followed by standardized postnatal care
Fetoscopic Endoluminal Tracheal Occlusion
prenatal balloon placement at 30-31+6 weeks and removal at 34-34+6 wks
Expectant management
expectant management during pregnancy followed by standardized neonatal care
No interventions assigned to this group
Interventions
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Fetoscopic Endoluminal Tracheal Occlusion
prenatal balloon placement at 30-31+6 weeks and removal at 34-34+6 wks
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
Exclusion Criteria
* 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
18 Years
FEMALE
No
Sponsors
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King's College Hospital NHS Trust (UK)
UNKNOWN
Hospital Clinic of Barcelona
OTHER
Hopital Antoine Beclere
OTHER
Hôpital Necker-Enfants Malades
OTHER
University Hospital, Bonn
OTHER
Mater Mothers' Hospital
OTHER
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
OTHER
Ospedale Pediatrico Bambino Gesù, Rome (IT)
UNKNOWN
Mount Sinai Hospital, Canada
OTHER
Baylor College of Medicine
OTHER
The University of Texas Health Science Center, Houston
OTHER
Medical University of Warsaw
OTHER
University Hospital, Gasthuisberg
OTHER
Responsible Party
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Jan Deprest
Jan Deprest, MD PhD, Professor in Obstetrics and Gynaecology
Principal Investigators
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Jan A Deprest, MD PhD
Role: STUDY_CHAIR
Universitaire Ziekenhuizen KU Leuven
Locations
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Baylor College of Medicine/Texas Children's Hospital
Houston, Texas, United States
University of Texas Health Science Center
Houston, Texas, United States
Mater Mother's Hospital
Brisbane, Queensland, Australia
University Hospitals Leuven
Leuven, , Belgium
Mount Sinai Hospital
Toronto, Ontario, Canada
Hôpital Antoine Béclère
Clamart, , France
Hôpital Necker - Enfants Malades
Paris, , France
University Hospital of Bonn
Bonn, , Germany
Ospedale Maggiore Policlinico
Milan, , Italy
Ospedale Pediatrico Bambino Gesù
Rome, , Italy
1st Department of Obstetrics and Gynecology, Medical University of Warsaw
Warsaw, , Poland
Hospital Clinic Barcelona
Barcelona, Catalonia, Spain
King's College Hospital
London, , United Kingdom
Countries
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References
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Jani J, Nicolaides KH, Keller RL, Benachi A, Peralta CF, Favre R, Moreno O, Tibboel D, Lipitz S, Eggink A, Vaast P, Allegaert K, Harrison M, Deprest J; Antenatal-CDH-Registry Group. Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol. 2007 Jul;30(1):67-71. doi: 10.1002/uog.4052.
Done E, Gucciardo L, Van Mieghem T, Jani J, Cannie M, Van Schoubroeck D, Devlieger R, Catte LD, Klaritsch P, Mayer S, Beck V, Debeer A, Gratacos E, Nicolaides K, Deprest J. Prenatal diagnosis, prediction of outcome and in utero therapy of isolated congenital diaphragmatic hernia. Prenat Diagn. 2008 Jul;28(7):581-91. doi: 10.1002/pd.2033.
Deprest J, Jani J, Gratacos E, Vandecruys H, Naulaers G, Delgado J, Greenough A, Nicolaides K; FETO Task Group. Fetal intervention for congenital diaphragmatic hernia: the European experience. Semin Perinatol. 2005 Apr;29(2):94-103. doi: 10.1053/j.semperi.2005.04.006.
Deprest J, Gratacos E, Nicolaides KH; FETO Task Group. Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results. Ultrasound Obstet Gynecol. 2004 Aug;24(2):121-6. doi: 10.1002/uog.1711.
Jani JC, Nicolaides KH, Gratacos E, Valencia CM, Done E, Martinez JM, Gucciardo L, Cruz R, Deprest JA. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009 Sep;34(3):304-10. doi: 10.1002/uog.6450.
Deprest JA, Gratacos E, Nicolaides K, Done E, Van Mieghem T, Gucciardo L, Claus F, Debeer A, Allegaert K, Reiss I, Tibboel D. Changing perspectives on the perinatal management of isolated congenital diaphragmatic hernia in Europe. Clin Perinatol. 2009 Jun;36(2):329-47, ix. doi: 10.1016/j.clp.2009.03.004.
Deprest JA, Hyett JA, Flake AW, Nicolaides K, Gratacos E. Current controversies in prenatal diagnosis 4: Should fetal surgery be done in all cases of severe diaphragmatic hernia? Prenat Diagn. 2009 Jan;29(1):15-9. doi: 10.1002/pd.2108. No abstract available.
Gregoir C, Engels AC, Gomez O, DeKoninck P, Lewi L, Gratacos E, Deprest JA. Fertility, pregnancy and gynecological outcomes after fetoscopic surgery for congenital diaphragmatic hernia. Hum Reprod. 2016 Sep;31(9):2024-30. doi: 10.1093/humrep/dew160. Epub 2016 Jul 4.
Snoek KG, Reiss IK, Greenough A, Capolupo I, Urlesberger B, Wessel L, Storme L, Deprest J, Schaible T, van Heijst A, Tibboel D; CDH EURO Consortium. Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update. Neonatology. 2016;110(1):66-74. doi: 10.1159/000444210. Epub 2016 Apr 15.
Nawapun K, Eastwood MP, Diaz-Cobos D, Jimenez J, Aertsen M, Gomez O, Claus F, Gratacos E, Deprest J. In vivo evidence by magnetic resonance volumetry of a gestational age dependent response to tracheal occlusion for congenital diaphragmatic hernia. Prenat Diagn. 2015 Nov;35(11):1048-56. doi: 10.1002/pd.4642. Epub 2015 Sep 29.
Deprest J, Brady P, Nicolaides K, Benachi A, Berg C, Vermeesch J, Gardener G, Gratacos E. Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial. Semin Fetal Neonatal Med. 2014 Dec;19(6):338-48. doi: 10.1016/j.siny.2014.09.006. Epub 2014 Nov 11.
Done E, Debeer A, Gucciardo L, Van Mieghem T, Lewi P, Devlieger R, De Catte L, Lewi L, Allegaert K, Deprest J. Prediction of neonatal respiratory function and pulmonary hypertension in fetuses with isolated congenital diaphragmatic hernia in the fetal endoscopic tracleal occlusion era: a single-center study. Fetal Diagn Ther. 2015;37(1):24-32. doi: 10.1159/000364805. Epub 2014 Nov 8.
DeKoninck P, Gomez O, Sandaite I, Richter J, Nawapun K, Eerdekens A, Ramirez JC, Claus F, Gratacos E, Deprest J. Right-sided congenital diaphragmatic hernia in a decade of fetal surgery. BJOG. 2015 Jun;122(7):940-6. doi: 10.1111/1471-0528.13065. Epub 2014 Sep 17.
Windrim R, Ryan G, Lebouthillier F, Campisi P, Kelly EN, Baud D, Yoo SJ, Deprest J. Development and use of a high-fidelity simulator for fetal endotracheal balloon occlusion (FETO) insertion and removal. Prenat Diagn. 2014 Feb;34(2):180-4. doi: 10.1002/pd.4284. Epub 2013 Dec 27.
Engels AC, DeKoninck P, van der Merwe JL, Van Mieghem T, Stevens P, Power B, Nicolaides KH, Gratacos E, Deprest JA. Does website-based information add any value in counseling mothers expecting a baby with severe congenital diaphragmatic hernia? Prenat Diagn. 2013 Nov;33(11):1027-32. doi: 10.1002/pd.4190. Epub 2013 Aug 29.
Dekoninck P, Gratacos E, Van Mieghem T, Richter J, Lewi P, Ancel AM, Allegaert K, Nicolaides K, Deprest J. Results of fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia and the set up of the randomized controlled TOTAL trial. Early Hum Dev. 2011 Sep;87(9):619-24. doi: 10.1016/j.earlhumdev.2011.08.001.
Deprest J, Flake A. How should fetal surgery for congenital diaphragmatic hernia be implemented in the post-TOTAL trial era: A discussion. Prenat Diagn. 2022 Mar;42(3):301-309. doi: 10.1002/pd.6091. Epub 2022 Jan 22.
Van Calster B, Benachi A, Nicolaides KH, Gratacos E, Berg C, Persico N, Gardener GJ, Belfort M, Ville Y, Ryan G, Johnson A, Sago H, Kosinski P, Bagolan P, Van Mieghem T, DeKoninck PLJ, Russo FM, Hooper SB, Deprest JA. The randomized Tracheal Occlusion To Accelerate Lung growth (TOTAL)-trials on fetal surgery for congenital diaphragmatic hernia: reanalysis using pooled data. Am J Obstet Gynecol. 2022 Apr;226(4):560.e1-560.e24. doi: 10.1016/j.ajog.2021.11.1351. Epub 2021 Nov 19.
Deprest JA, Benachi A, Gratacos E, Nicolaides KH, Berg C, Persico N, Belfort M, Gardener GJ, Ville Y, Johnson A, Morini F, Wielgos M, Van Calster B, DeKoninck PLJ; TOTAL Trial for Moderate Hypoplasia Investigators. Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia. N Engl J Med. 2021 Jul 8;385(2):119-129. doi: 10.1056/NEJMoa2026983. Epub 2021 Jun 8.
Related Links
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website on prenatal diagnosis and management of CDH of the FETO consortium
website of this trial on prenatal management of CDH
same as www.euroCDH.org
same as totaltrial.eu
Other Identifiers
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2008-4634
Identifier Type: OTHER
Identifier Source: secondary_id
ML4999- B32220084540
Identifier Type: OTHER
Identifier Source: secondary_id
B32220084540
Identifier Type: -
Identifier Source: org_study_id