'TOTAL' (Tracheal Occlusion To Accelerate Lung Growth) Trial

NCT02875860 | Completed Phase 2 Results DMC FDA Device

• 1 other identifier: H-39398
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will test whether temporary fetoscopic endoluminal tracheal occlusion (FETO) rather than expectant management during pregnancy, followed by standardized postnatal management, increases survival at discharge and decreases oxygen need at 6 months in case of survival till discharge.

Conditions

Hernia; Hernia, Diaphragmatic; Hernia, DIaphragmatic, Congenital; Pathological Conditions, Anatomical; Congenital Abnormalities; Congenital Diaphragmatic Hernia; Fetal Anomaly; Fetal Surgery; Pulmonary Hypoplasia

Keywords

CDH; Congenital Diaphragmatic Hernia; Fetal Tracheal Occlusion; FETO; plug-unplug; GoldBal2; Balloon; Goldvalve Balloon; TOTAL

Outcome Measures

Primary Outcomes (2)

• Proportion of Neonate Survival at Discharge From Hospital

  The null hypothesis to be tested is that there is no difference in survival between fetuses managed expectantly during pregnancy versus those undergoing antenatal therapy (FETO).

  At hospital discharge, an average of 1.5 months

• Participants Requiring Supplemental Oxygen

  The number of survivors requiring supplemental oxygen at 6 months of age

  At 6 months of age

Secondary Outcomes (15)

• Grade of Oxygen Dependency

  at 6 months of age

• Occurrence of Severe Pulmonary Hypertension

  During the first 4 weeks of life (neonatal period).

• ECMO (Extracorporeal Membrane Oxygenation) Support

  Neonatal period (during the first 4 weeks of life)

• CDH Defect Size

  Measured in neonate at delivery by MRI and/or ultrasound

• Number of Days in the NICU

  At the time of discharge from the NICU, an average of 1.5 months

Study Arms (2)

Standardized postnatal care (Expectant)

OTHER

Mothers will be expectantly managed during pregnancies and babies receive standardized postnatal care at a tertiary center used to manage babies with CDH. The recommendation is that they adhere to consensus guidelines published on the study website.

Other: Standardized postnatal care

Prenatal Intervention (FETO)

EXPERIMENTAL

Patients will undergo fetoscopic endoluminal tracheal occlusion and ideally prenatal reversal of the occlusion followed by standardized postnatal care as in the expectant . In this study FETO (where GoldBal2 detachable balloon and Baltaccidbpe100 Delivery Catheter are used) is to be done between 30 weeks plus 0 day and 31 weeks plus 6 days and removal of the balloon at 34 weeks plus 0 day to 34 weeks plus 6 days.

Device: GoldBal2 detachable balloon; Device: Baltaccidbpe100 Delivery Catheter; Other: Standardized postnatal care

Interventions

GoldBal2 detachable balloon DEVICE

Placement of the balloon using the plug/unplug method.

Prenatal Intervention (FETO)

Baltaccidbpe100 Delivery Catheter DEVICE

The catheter assists with implanting the balloon in the plug/unplug method.

Prenatal Intervention (FETO)

Standardized postnatal care OTHER

After birth, the babies will receive standardized postnatal care at a tertiary center used to manage babies with CDH. The recommendation is that they adhere to consensus guidelines published on the study website. For detailed description on this please visit https://www.karger.com/Article/Abstract/320622

Prenatal Intervention (FETO); Standardized postnatal care (Expectant)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients aged 18 years or more, who are able to consent,
• Singleton pregnancy,
• Chromosomally normal fetus,
• Gestation at randomization prior to 31 weeks plus 5 days or so that occlusion is done at the latest on 31 weeks plus 6 days,
• Fetus is 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.
• The O/E LHR will be determined by the FETO centers as follows:
• Measurement of the contralateral lung area preferentially by the tracing method at the 4-chamber view of the heart; if by other method adjusted normative ranges must be used.
• Measurement of the head circumference at the standard biparietal view of the head
• The observed lung area: calculation of the LHR as the ratio of the measurements of the lung area to head circumference
• The expected lung area is the lung area of a normal gestational age match, as determined by the head circumference of the index case in a normogram established for the same measurement method (tracing method in this case). A calculator for this will be available on the website of the study.
• Calculation of the observed over expected lung area,
• Acceptance of randomization and the consequences for the further management during pregnancy and thereafter, this includes the required observation following FETO surgery, which lasts up to 4 weeks after balloon is in place,
• 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," and
• Provide written consent to participate.

You may not qualify if:

• Maternal contraindication to fetoscopic surgery or severe medical condition in pregnancy that make fetal intervention risky,
• 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 labor, cervix shortened (\<15 mm at randomization) or uterine anomaly strongly predisposing to preterm labor, placenta previa,
• Patient age less than 18 years,
• Psychosocial ineligibility, precluding consent,
• Patient refusing randomization, to comply with required 4-week observation after balloon placement, or to comply with return to FETO center during the time period the airways are occluded or for elective removal of the balloon.
• Patient allergic to latex.

Sponsors & Collaborators

• Michael A Belfort: lead
• Baylor College of Medicine: collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (1)

Baylor College of Medicine/Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (16)

• 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.

  PMID: 17587219 BACKGROUND

• Jani JC, Benachi A, Nicolaides KH, Allegaert K, Gratacos E, Mazkereth R, Matis J, Tibboel D, Van Heijst A, Storme L, Rousseau V, Greenough A, Deprest JA; Antenatal-CDH-Registry group. Prenatal prediction of neonatal morbidity in survivors with congenital diaphragmatic hernia: a multicenter study. Ultrasound Obstet Gynecol. 2009 Jan;33(1):64-9. doi: 10.1002/uog.6141.

  PMID: 18844275 BACKGROUND

• 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.

  PMID: 15287047 BACKGROUND

• Jani J, Nicolaides K, Gratacos E, et al. 558: Short term neonatal morbidity in severe left-sided congenital diaphragmatic hernia treated by tracheal occlusion before 30 weeks. Am J Obstet Gynecol Dec;197(6),Supplement:S162.

  BACKGROUND

• Jani JC, Nicolaides KH, Gratacos E, Vandecruys H, Deprest JA; FETO Task Group. Fetal lung-to-head ratio in the prediction of survival in severe left-sided diaphragmatic hernia treated by fetal endoscopic tracheal occlusion (FETO). Am J Obstet Gynecol. 2006 Dec;195(6):1646-50. doi: 10.1016/j.ajog.2006.04.004. Epub 2006 Jun 12.

  PMID: 16769018 BACKGROUND

• 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.

  PMID: 19658113 BACKGROUND

• Cannie MM, Jani JC, De Keyzer F, Allegaert K, Dymarkowski S, Deprest J. Evidence and patterns in lung response after fetal tracheal occlusion: clinical controlled study. Radiology. 2009 Aug;252(2):526-33. doi: 10.1148/radiol.2522081955. Epub 2009 Jun 9.

  PMID: 19508989 BACKGROUND

• Reiss I, Schaible T, van den Hout L, Capolupo I, Allegaert K, van Heijst A, Gorett Silva M, Greenough A, Tibboel D; CDH EURO Consortium. Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: the CDH EURO Consortium consensus. Neonatology. 2010;98(4):354-64. doi: 10.1159/000320622. Epub 2010 Oct 27.

  PMID: 20980772 BACKGROUND

• Snoek KG, Capolupo I, van Rosmalen J, Hout Lde J, Vijfhuize S, Greenough A, Wijnen RM, Tibboel D, Reiss IK; CDH EURO Consortium. Conventional Mechanical Ventilation Versus High-frequency Oscillatory Ventilation for Congenital Diaphragmatic Hernia: A Randomized Clinical Trial (The VICI-trial). Ann Surg. 2016 May;263(5):867-74. doi: 10.1097/SLA.0000000000001533.

  PMID: 26692079 BACKGROUND

• Deprest JA, Flemmer AW, Gratacos E, Nicolaides K. Antenatal prediction of lung volume and in-utero treatment by fetal endoscopic tracheal occlusion in severe isolated congenital diaphragmatic hernia. Semin Fetal Neonatal Med. 2009 Feb;14(1):8-13. doi: 10.1016/j.siny.2008.08.010. Epub 2008 Oct 8.

  PMID: 18845492 BACKGROUND

• Ruano R, Aubry MC, Barthe B, Mitanchez D, Dumez Y, Benachi A. Quantitative analysis of fetal pulmonary vasculature by 3-dimensional power Doppler ultrasonography in isolated congenital diaphragmatic hernia. Am J Obstet Gynecol. 2006 Dec;195(6):1720-8. doi: 10.1016/j.ajog.2006.05.010. Epub 2006 Jun 12.

  PMID: 16769020 BACKGROUND

• Ostrea EM, Villanueva-Uy ET, Natarajan G, Uy HG. Persistent pulmonary hypertension of the newborn: pathogenesis, etiology, and management. Paediatr Drugs. 2006;8(3):179-88. doi: 10.2165/00148581-200608030-00004.

  PMID: 16774297 BACKGROUND

• Congenital Diaphragmatic Hernia Study Group; Lally KP, Lally PA, Lasky RE, Tibboel D, Jaksic T, Wilson JM, Frenckner B, Van Meurs KP, Bohn DJ, Davis CF, Hirschl RB. Defect size determines survival in infants with congenital diaphragmatic hernia. Pediatrics. 2007 Sep;120(3):e651-7. doi: 10.1542/peds.2006-3040.

  PMID: 17766505 BACKGROUND

• Gallot D, Boda C, Ughetto S, Perthus I, Robert-Gnansia E, Francannet C, Laurichesse-Delmas H, Jani J, Coste K, Deprest J, Labbe A, Sapin V, Lemery D. Prenatal detection and outcome of congenital diaphragmatic hernia: a French registry-based study. Ultrasound Obstet Gynecol. 2007 Mar;29(3):276-83. doi: 10.1002/uog.3863.

  PMID: 17177265 BACKGROUND

• Deprest JA, Evrard VA, Verbeken EK, Perales AJ, Delaere PR, Lerut TE, Flageole H. Tracheal side effects of endoscopic balloon tracheal occlusion in the fetal lamb model. Eur J Obstet Gynecol Reprod Biol. 2000 Sep;92(1):119-26. doi: 10.1016/s0301-2115(00)00435-8.

  PMID: 10986445 BACKGROUND

• Chiba T, Albanese CT, Farmer DL, Dowd CF, Filly RA, Machin GA, Harrison M. Balloon tracheal occlusion for congenital diaphragmatic hernia: experimental studies. J Pediatr Surg. 2000 Nov;35(11):1566-70. doi: 10.1053/jpsu.2000.18311.

  PMID: 11083424 BACKGROUND

Related Links

• Information for the public and healthcare providers.
• Information for the public and healthcare providers.

MeSH Terms

Conditions

Hernia; Hernia, Diaphragmatic; Pathological Conditions, Anatomical; Congenital Abnormalities; Hernias, Diaphragmatic, Congenital

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms; Internal Hernia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Dr. Michael Belfort
• Organization: Baylor College of Medicine

belfort@bcm.edu

832-826-7375

Study Officials

• Michael Belfort, MD, PhD

  Baylor College of Medicine - Texas Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 5, 2016
• First Posted: August 23, 2016
• Study Start: January 1, 2017
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: June 23, 2022
• Results First Posted: June 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)