Tracheal Occlusion To Accelerate Lung Growth (TOTAL) Trial for Severe Pulmonary Hypoplasia

Diaphragmatic Hernia Clinical Trial

— TOTAL  

Official title:

Randomized Trial of Fetoscopic Endoluminal Tracheal Occlusion (FETO) Versus Expectant Management During Pregnancy in Fetuses With Left Sided and Isolated Congenital Diaphragma Hernia and Severe Pulmonary Hypoplasia.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01240057
• Other study ID #: ML 6277
• Secondary ID: B32220108118
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: November 2011
• Est. completion date: December 2020

Study information

• Verified date: May 2021
• Source: University Hospital, Gasthuisberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial investigates whether prenatal intervention improves survival rate of fetuses with isolated congenital diaphragmatic hernia and severe pulmonary hypoplasia, as compared to expectant management during pregnancy, both followed by standardized postnatal care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: December 2020
• Est. primary completion date: March 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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 29 wks plus 5 d (so that occlusion is done at the latest on 29 wks plus 6 d)

• Estimated to have severe pulmonary hypoplasia, defined prenatally as: O/E LHR <25 %, irrespective of the liver position

• 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

Related Conditions & MeSH terms

• Congenital Diseases
• Diaphragmatic Hernia
• Hernia
• Hernia, Diaphragmatic
• Hernias, Diaphragmatic, Congenital
• Pulmonary Hypoplasia

Intervention

Procedure:
• fetal endoluminal tracheal occlusion
percutaneous fetoscopy, positioning of endoluminal balloon at 27-30 weeks and whenever possible elective removal at 34 weeks

Other:
• watchful waiting during pregnancy
pregnancy surveillance for fetal wellbeing, development of polyhydramnios and cervical shortening

Locations

Country	Name	City	State
Australia	Mater Mother's Hospital	Brisbane	Queensland
Belgium	University Hospitals Leuven	Leuven
Canada	Mount Sinai Hospital	Toronto	Ontario
France	Hôpital Antoine Béclère	Clamart
Germany	University Hospital of Bonn	Bonn
Italy	Ospedale Maggiore Policlinico	Milano
Italy	Ospedale Pediatrico Bambino Gesù	Rome
Japan	National Center for Child Health and Development	Tokyo
Poland	1st Department of Obstetrics and Gynecology, Medical University of Warsaw	Warsaw
Spain	Hospital Clinic Barcelona	Barcelona	Catalunya
United Kingdom	King's College Hospital	London
United States	University of Texas Health Science Center	Houston	Texas

Sponsors (12)

Lead Sponsor

Collaborator

University Hospital, Gasthuisberg

1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Hopital Antoine Beclere, Hospital Clinic of Barcelona, King's College Hospital NHS Trust (UK), Mater Mothers' Hospital, Mount Sinai Hospital, Canada, National Center for Child Health and Development, Tokyo (JP), Ospedale Pediatrico Bambino Gesù, Rome (IT), The University of Texas Health Science Center, Houston, University Hospital, Bonn

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Japan,  Poland,  Spain,  United Kingdom, 

References & Publications (10)

Deprest J, Breysem L, Gratacos E, Nicolaides K, Claus F, Debeer A, Smet MH, Proesmans M, Fayoux P, Storme L. Tracheal side effects following fetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia. Pediatr Radiol. 2010 May;40(5):670-3. doi: 10.1007/s00247-010-1579-9. Epub 2010 Mar 30. — View Citation

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. Erratum in: Ultrasound Obstet Gynecol. 2004 Oct;24(5):594. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Jani J, Keller RL, Benachi A, Nicolaides KH, Favre R, Gratacos E, Laudy J, Eisenberg V, Eggink A, Vaast P, Deprest J; Antenatal-CDH-Registry Group. Prenatal prediction of survival in isolated left-sided diaphragmatic hernia. Ultrasound Obstet Gynecol. 2006 Jan;27(1):18-22. — View Citation

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. — View Citation

Jani JC, Benachi A, Nicolaides KH, Allegaert K, Gratacós 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. — View Citation

Jani JC, Nicolaides KH, Gratacós E, Valencia CM, Doné 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. — View Citation

Rodrigues HC, Deprest J, v d Berg PP. When referring physicians and researchers disagree on equipoise: the TOTAL trial experience. Prenat Diagn. 2011 Jun;31(6):589-94. doi: 10.1002/pd.2756. Epub 2011 Apr 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival at discharge from neonatal intensive care unit	The baby can be discharged either alive (and then it qualifies as "surviving at discharge") or dead. Not discharged babies have not reached the primary endpoint.	at discharge from neonatal intensive care unit
Secondary	prenatal increase in lung volume after FETO	volume of lung after occlusion	prior to balloon removal
Secondary	grading of oxygen dependency		born >32 wks: between 28-56d of life; born <32wks: 36wks postmenstrual age
Secondary	occurrence of pulmonary hypertension	determined by cardiac ultrasound	within first weeks of life
Secondary	number of days in Neonatal Intensive Care Unit (NICU)	As long as the baby is in the hospital, it is hospitalized either in NICU or in another, less intensive care unit.; The number of days in NICU is an outcome variable, expressed in days.	within hospital stay
Secondary	number of days of ventilatory support		within NICU stay
Secondary	presence of periventricular leucomalacia		2 months of life
Secondary	presence of neonatal sepsis, intraventricular haemorrhage, retinopathy grade III or higher		within hospital stay
Secondary	number of days till full enteral feeding		within first 2 years of life
Secondary	presence of gastro-esophagal reflux		at discharge
Secondary	day of surgery		within hospital stay
Secondary	requirement for use of patch for repair		at the time of postnatal surgery
Secondary	bronchopulmonary dysplasia	defined as oxygen need for at least 28 days	with the first 8 weeks
Secondary	Need for Extracorporeal membrane oxygenation		during NICU admission
Secondary	Defect size		at the time of postnatal surgery
Secondary	number of days alive in case of postnatal death		during NICU admission

External Links

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