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

NCT ID: NCT02875860

Last Updated: 2022-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-10-31

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.

Detailed Description

This is a multi-center, non-blinded randomized controlled trial in fetuses with isolated moderate CDH, i.e. moderate lung hypoplasia (as determined by prenatal assessment of lung development). It essentially compares fetal therapy added to conventional postnatal care, versus expectant prenatal management during pregnancy followed by conventional postnatal care.

Enrollment:

Following completion of an inclusion/exclusion criteria checklist and obtaining informed consent, the subject will be randomized into two groups ("FETO" and "expectant").

Procedures:

Group I: Standardized postnatal care (expectant group): 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.

Group II: Prenatal intervention (FETO group): patients will undergo fetoscopic tracheal occlusion and ideally prenatal reversal of the occlusion followed by standardized postnatal care as in I. In this study FETO 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.

This study trial is a pragmatical or efficacy trial: ideally mothers will deliver after removal of the balloon at those tertiary centers, typically offering postnatal care for the patient involved. In group II (FETO-group), mothers will, in between placement and removal of the balloon, thus carrying a fetus with obstructed airways, ideally remain under the care of our local fetal treatment center (further referred to as FETO center). As many as possible precautions are taken to avoid problems with balloon removal in case of earlier than expected delivery.

• Balloons are to be electively removed prior to 35 weeks. FETO centers will provide 24/24 hours and 7/7 days services for management of fetuses with obstructed airways, either in utero or during labor and delivery.
• Patients in the study and randomized to FETO, will be encouraged to stay near the FETO center. After reversal of the occlusion the patient will be referred to the tertiary care center where delivery and postnatal care will be undertaken. If the patient is not remaining at or close to the FETO center, the postnatal treatment center should organize likewise EXIT services.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standardized postnatal care (Expectant)

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.

Group Type: OTHER

Standardized postnatal care

Intervention Type: 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)

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.

Group Type: EXPERIMENTAL

GoldBal2 detachable balloon

Intervention Type: DEVICE

Placement of the balloon using the plug/unplug method.

Baltaccidbpe100 Delivery Catheter

Intervention Type: DEVICE

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

Standardized postnatal care

Intervention Type: 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

Interventions

GoldBal2 detachable balloon

Placement of the balloon using the plug/unplug method.

Intervention Type: DEVICE

Baltaccidbpe100 Delivery Catheter

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

Intervention Type: DEVICE

Standardized postnatal care

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Patients aged 18 years or more, who are able to consent,

2. Singleton pregnancy,

3. Chromosomally normal fetus,

4. 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,

5. 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,

6. 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,

7. 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

8. Provide written consent to participate.

9. Fetus with no major anomalies that would impact the clinical course or outcomes.

7. 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.

8. Patient allergic to latex.

Exclusion Criteria

1. Maternal contraindication to fetoscopic surgery or severe medical condition in pregnancy that make fetal intervention risky,

2. Technical limitations precluding fetoscopic surgery, such as severe maternal obesity, uterine fibroids or potentially others, not anticipated at the time of writing this protocol,

3. Preterm labor, cervix shortened (<15 mm at randomization) or uterine anomaly strongly predisposing to preterm labor, placenta previa,

4. Patient age less than 18 years,

5. Psychosocial ineligibility, precluding consent,

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: collaborator

Michael A Belfort

OTHER

Sponsor Role: lead

Responsible Party

Michael A Belfort

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael Belfort, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine - Texas Children's Hospital

Locations

Baylor College of Medicine/Texas Children's Hospital

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17587219 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18844275 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15287047 (View on PubMed)

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.

Reference Type: 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.

Reference Type: BACKGROUND

PMID: 16769018 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19658113 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19508989 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20980772 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26692079 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18845492 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16769020 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16774297 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17766505 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17177265 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10986445 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11083424 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.TOTALtrial.eu

Information for the public and healthcare providers.

http://www.euroCDH.org

Information for the public and healthcare providers.

Other Identifiers

H-39398

Identifier Type: -

Identifier Source: org_study_id