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

NCT ID: NCT01240057

Last Updated: 2021-05-04

Study Results

Results pending

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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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

93 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Study Completion Date

2020-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Congenital Diseases Diaphragmatic Hernia Pulmonary Hypoplasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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expectant management during pregnancy

watchful waiting during pregnancy

Group Type PLACEBO_COMPARATOR

watchful waiting during pregnancy

Intervention Type OTHER

pregnancy surveillance for fetal wellbeing, development of polyhydramnios and cervical shortening

fetal endoluminal tracheal occlusion

fetoscopic balloon occlusion at 27 to 29+6 weeks of gestation

Group Type EXPERIMENTAL

fetal endoluminal tracheal occlusion

Intervention Type PROCEDURE

percutaneous fetoscopy, positioning of endoluminal balloon at 27-30 weeks and whenever possible elective removal at 34 weeks

Interventions

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fetal endoluminal tracheal occlusion

percutaneous fetoscopy, positioning of endoluminal balloon at 27-30 weeks and whenever possible elective removal at 34 weeks

Intervention Type PROCEDURE

watchful waiting during pregnancy

pregnancy surveillance for fetal wellbeing, development of polyhydramnios and cervical shortening

Intervention Type OTHER

Other Intervention Names

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Balt Goldbal 2 balloon

Eligibility Criteria

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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

* 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

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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King's College Hospital NHS Trust (UK)

UNKNOWN

Sponsor Role collaborator

Hospital Clinic of Barcelona

OTHER

Sponsor Role collaborator

Hopital Antoine Beclere

OTHER

Sponsor Role collaborator

University Hospital, Bonn

OTHER

Sponsor Role collaborator

Mater Mothers' Hospital

OTHER

Sponsor Role collaborator

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

OTHER

Sponsor Role collaborator

Ospedale Pediatrico Bambino Gesù, Rome (IT)

UNKNOWN

Sponsor Role collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role collaborator

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

UNKNOWN

Sponsor Role collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role collaborator

Medical University of Warsaw

OTHER

Sponsor Role collaborator

University Hospital, Gasthuisberg

OTHER

Sponsor Role lead

Responsible Party

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Jan Deprest

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jan Deprest, MD

Role: PRINCIPAL_INVESTIGATOR

Universitaire Ziekenhuizen KU Leuven

Locations

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University of Texas Health Science Center

Houston, Texas, United States

Site Status

Mater Mother's Hospital

Brisbane, Queensland, Australia

Site Status

University Hospitals Leuven

Leuven, , Belgium

Site Status

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status

Hôpital Antoine Béclère

Clamart, , France

Site Status

University Hospital of Bonn

Bonn, , Germany

Site Status

Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Ospedale Pediatrico Bambino Gesù

Rome, , Italy

Site Status

National Center for Child Health and Development

Tokyo, , Japan

Site Status

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

Warsaw, , Poland

Site Status

Hospital Clinic Barcelona

Barcelona, Catalonia, Spain

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Countries

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

References

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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)

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. No abstract available.

Reference Type BACKGROUND
PMID: 20352401 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19559323 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19125386 (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)

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)

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 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. doi: 10.1002/uog.2688.

Reference Type BACKGROUND
PMID: 16374756 (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)

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.

Reference Type BACKGROUND
PMID: 21484841 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35032132 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34808130 (View on PubMed)

Deprest JA, Nicolaides KH, Benachi A, Gratacos E, Ryan G, Persico N, Sago H, Johnson A, Wielgos M, Berg C, Van Calster B, Russo FM; TOTAL Trial for Severe Hypoplasia Investigators. Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia. N Engl J Med. 2021 Jul 8;385(2):107-118. doi: 10.1056/NEJMoa2027030. Epub 2021 Jun 8.

Reference Type DERIVED
PMID: 34106556 (View on PubMed)

Related Links

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http://www.totaltrial.eu

opens only end 2010

Other Identifiers

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B32220108118

Identifier Type: OTHER

Identifier Source: secondary_id

ML 6277

Identifier Type: -

Identifier Source: org_study_id

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