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

• ClinicalTrials.gov Identifier: NCT01240057
• Recruitment Status: Active, not recruiting
• First Posted: November 15, 2010
• Last Update Posted: November 24, 2020
• Sponsor: University Hospital, Gasthuisberg
• Collaborators: King's College Hospital NHS Trust (UK); Hospital Clinic of Barcelona; Hopital Antoine Beclere; University Hospital, Bonn; Mater Mothers' Hospital; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Ospedale Pediatrico Bambino Gesù, Rome (IT); Mount Sinai Hospital, Canada; National Center for Child Health and Development, Tokyo (JP); The University of Texas Health Science Center, Houston; 1st Department of Obstetrics and Gynecology, Medical University of Warsaw
• Information provided by (Responsible Party): Jan Deprest, University Hospital, Gasthuisberg

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Congenital Diseases; Diaphragmatic Hernia; Pulmonary Hypoplasia	Procedure: fetal endoluminal tracheal occlusion; Other: watchful waiting during pregnancy	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 93 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Study Start Date: November 2011
• Actual Primary Completion Date: March 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: expectant management during pregnancy; watchful waiting during pregnancy	Other: watchful waiting during pregnancy; pregnancy surveillance for fetal wellbeing, development of polyhydramnios and cervical shortening
Experimental: fetal endoluminal tracheal occlusion; fetoscopic balloon occlusion at 27 to 29+6 weeks of gestation	Procedure: fetal endoluminal tracheal occlusion; percutaneous fetoscopy, positioning of endoluminal balloon at 27-30 weeks and whenever possible elective removal at 34 weeks; Other Name: Balt Goldbal 2 balloon

Outcome Measures

Primary Outcome Measures :

1. Survival at discharge from neonatal intensive care unit [ Time Frame: 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.

Secondary Outcome Measures :

1. prenatal increase in lung volume after FETO [ Time Frame: prior to balloon removal ]
   volume of lung after occlusion
2. grading of oxygen dependency [ Time Frame: born >32 wks: between 28-56d of life; born <32wks: 36wks postmenstrual age ]
3. occurrence of pulmonary hypertension [ Time Frame: within first weeks of life ]
   determined by cardiac ultrasound
4. number of days in Neonatal Intensive Care Unit (NICU) [ Time Frame: within hospital stay ]

   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.

5. number of days of ventilatory support [ Time Frame: within NICU stay ]
6. presence of periventricular leucomalacia [ Time Frame: 2 months of life ]
7. presence of neonatal sepsis, intraventricular haemorrhage, retinopathy grade III or higher [ Time Frame: within hospital stay ]
8. number of days till full enteral feeding [ Time Frame: within first 2 years of life ]
9. presence of gastro-esophagal reflux [ Time Frame: at discharge ]
10. day of surgery [ Time Frame: within hospital stay ]
11. requirement for use of patch for repair [ Time Frame: at the time of postnatal surgery ]
12. bronchopulmonary dysplasia [ Time Frame: with the first 8 weeks ]
    defined as oxygen need for at least 28 days
13. Need for Extracorporeal membrane oxygenation [ Time Frame: during NICU admission ]
14. Defect size [ Time Frame: at the time of postnatal surgery ]
15. number of days alive in case of postnatal death [ Time Frame: during NICU admission ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Texas

University of Texas Health Science Center

Houston, Texas, United States, 77030

Australia, Queensland

Mater Mother's Hospital

Brisbane, Queensland, Australia, 4101

Belgium

University Hospitals Leuven

Leuven, Belgium, 3000

Canada, Ontario

Mount Sinai Hospital

Toronto, Ontario, Canada, M5G 1X5

France

Hôpital Antoine Béclère

Clamart, France, 92141

Germany

University Hospital of Bonn

Bonn, Germany, 53105

Italy

Ospedale Maggiore Policlinico

Milano, Italy, 20122

Ospedale Pediatrico Bambino Gesù

Rome, Italy, 00123

Japan

National Center for Child Health and Development

Tokyo, Japan, 157-8535

Poland

1st Department of Obstetrics and Gynecology, Medical University of Warsaw

Warsaw, Poland

Spain

Hospital Clinic Barcelona

Barcelona, Catalunya, Spain, 08028

United Kingdom

King's College Hospital

London, United Kingdom, SE5 9RS

Sponsors and Collaborators

University Hospital, Gasthuisberg

King's College Hospital NHS Trust (UK)

Hospital Clinic of Barcelona

Hopital Antoine Beclere

University Hospital, Bonn

Mater Mothers' Hospital

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Ospedale Pediatrico Bambino Gesù, Rome (IT)

Mount Sinai Hospital, Canada

National Center for Child Health and Development, Tokyo (JP)

The University of Texas Health Science Center, Houston

1st Department of Obstetrics and Gynecology, Medical University of Warsaw

Investigators

• Principal Investigator: Jan Deprest, MD; Universitaire Ziekenhuizen Leuven

More Information

Additional Information:

opens only end 2010 

Publications:

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

• Responsible Party: Jan Deprest, MD, PhD, University Hospital, Gasthuisberg
• ClinicalTrials.gov Identifier: NCT01240057
• Other Study ID Numbers: ML 6277; B32220108118 ( Other Identifier: UZ Gasthuisberg KU Leuven (Belgium) )
• First Posted: November 15, 2010
• Last Update Posted: November 24, 2020
• Last Verified: November 2020

Keywords provided by Jan Deprest, University Hospital, Gasthuisberg:

Isolated Congenital Diaphragmatic Hernia; Fetal Surgery; Pulmonary Hypoplasia

Additional relevant MeSH terms:

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