Ignite Creation Date:
2025-12-24 @ 6:58 PM
Ignite Modification Date:
2025-12-31 @ 4:05 AM
Study NCT ID:
NCT01240057
Status:
COMPLETED
Last Update Posted:
2021-05-04
First Post:
2010-08-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Tracheal Occlusion To Accelerate Lung Growth (TOTAL) Trial for Severe Pulmonary Hypoplasia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D006548', 'term': 'Hernia, Diaphragmatic'}], 'ancestors': [{'id': 'D000082122', 'term': 'Internal Hernia'}, {'id': 'D006547', 'term': 'Hernia'}, {'id': 'D020763', 'term': 'Pathological Conditions, Anatomical'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2', 'PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 93}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-05', 'completionDateStruct': {'date': '2020-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-05-03', 'studyFirstSubmitDate': '2010-08-04', 'studyFirstSubmitQcDate': '2010-11-12', 'lastUpdatePostDateStruct': {'date': '2021-05-04', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2010-11-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2020-03', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Survival at discharge from neonatal intensive care unit', 'timeFrame': 'at discharge from neonatal intensive care unit', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'prenatal increase in lung volume after FETO', 'timeFrame': 'prior to balloon removal', 'description': 'volume of lung after occlusion'}, {'measure': 'grading of oxygen dependency', 'timeFrame': 'born >32 wks: between 28-56d of life; born <32wks: 36wks postmenstrual age'}, {'measure': 'occurrence of pulmonary hypertension', 'timeFrame': 'within first weeks of life', 'description': 'determined by cardiac ultrasound'}, {'measure': 'number of days in Neonatal Intensive Care Unit (NICU)', 'timeFrame': 'within hospital stay', 'description': 'As long as the baby is in the hospital, it is hospitalized either in NICU or in another, less intensive care unit.\n\nThe number of days in NICU is an outcome variable, expressed in days.'}, {'measure': 'number of days of ventilatory support', 'timeFrame': 'within NICU stay'}, {'measure': 'presence of periventricular leucomalacia', 'timeFrame': '2 months of life'}, {'measure': 'presence of neonatal sepsis, intraventricular haemorrhage, retinopathy grade III or higher', 'timeFrame': 'within hospital stay'}, {'measure': 'number of days till full enteral feeding', 'timeFrame': 'within first 2 years of life'}, {'measure': 'presence of gastro-esophagal reflux', 'timeFrame': 'at discharge'}, {'measure': 'day of surgery', 'timeFrame': 'within hospital stay'}, {'measure': 'requirement for use of patch for repair', 'timeFrame': 'at the time of postnatal surgery'}, {'measure': 'bronchopulmonary dysplasia', 'timeFrame': 'with the first 8 weeks', 'description': 'defined as oxygen need for at least 28 days'}, {'measure': 'Need for Extracorporeal membrane oxygenation', 'timeFrame': 'during NICU admission'}, {'measure': 'Defect size', 'timeFrame': 'at the time of postnatal surgery'}, {'measure': 'number of days alive in case of postnatal death', 'timeFrame': 'during NICU admission'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Isolated Congenital Diaphragmatic Hernia', 'Fetal Surgery', 'Pulmonary Hypoplasia'], 'conditions': ['Congenital Diseases', 'Diaphragmatic Hernia', 'Pulmonary Hypoplasia']}, 'referencesModule': {'references': [{'pmid': '19658113', 'type': 'BACKGROUND', 'citation': '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': '20352401', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '19559323', 'type': 'BACKGROUND', '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.'}, {'pmid': '19125386', 'type': 'BACKGROUND', '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. No abstract available.'}, {'pmid': '18845492', 'type': 'BACKGROUND', '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.'}, {'pmid': '18844275', 'type': 'BACKGROUND', 'citation': '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': '17587219', 'type': 'BACKGROUND', '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. doi: 10.1002/uog.4052.'}, {'pmid': '16374756', 'type': 'BACKGROUND', '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. doi: 10.1002/uog.2688.'}, {'pmid': '15287047', 'type': 'BACKGROUND', '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. doi: 10.1002/uog.1711.'}, {'pmid': '21484841', 'type': 'BACKGROUND', '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.'}, {'pmid': '35032132', 'type': 'DERIVED', 'citation': '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.'}, {'pmid': '34808130', 'type': 'DERIVED', 'citation': '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.'}, {'pmid': '34106556', 'type': 'DERIVED', 'citation': '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.'}], 'seeAlsoLinks': [{'url': 'http://www.totaltrial.eu', 'label': 'opens only end 2010'}]}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT'], 'maximumAge': '50 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients aged 18 years or more, who are able to consent\n* Singleton pregnancy\n* Anatomically and chromosomally normal fetus\n* Left sided diaphragmatic hernia\n* Gestation at randomization prior to 29 wks plus 5 d (so that occlusion is done at the latest on 29 wks plus 6 d)\n* Estimated to have severe pulmonary hypoplasia, defined prenatally as: O/E LHR \\<25 %, irrespective of the liver position\n* Acceptance of randomization and the consequences for the further management during pregnancy and thereafter.\n* 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.\n* Intended postnatal treatment center must subscribe to suggested guidelines for "standardized postnatal treatment".\n* Provide written consent to participate in this RCT\n\nExclusion Criteria:\n\n* Maternal contraindication to fetoscopic surgery or severe medical condition in pregnancy that make fetal intervention risk full\n* Technical limitations precluding fetoscopic surgery, such as severe maternal obesity, uterine fibroids or potentially others, not anticipated at the time of writing this protocol.\n* Preterm labour, cervix shortened (\\<15 mm at randomization) or uterine anomaly strongly predisposing to preterm labour, placenta previa\n* Patient age less than 18 years\n* Psychosocial ineligibility, precluding consent\n* Diaphragmatic hernia: right-sided or bilateral, major anomalies, isolated left-sided outside the O/E LHR limits for the inclusion criteria\n* 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'}, 'identificationModule': {'nctId': 'NCT01240057', 'acronym': 'TOTAL', 'briefTitle': 'Tracheal Occlusion To Accelerate Lung Growth (TOTAL) Trial for Severe Pulmonary Hypoplasia', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Gasthuisberg'}, 'officialTitle': '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.', 'orgStudyIdInfo': {'id': 'ML 6277'}, 'secondaryIdInfos': [{'id': 'B32220108118', 'type': 'OTHER', 'domain': 'UZ Gasthuisberg KU Leuven (Belgium)'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'expectant management during pregnancy', 'description': 'watchful waiting during pregnancy', 'interventionNames': ['Other: watchful waiting during pregnancy']}, {'type': 'EXPERIMENTAL', 'label': 'fetal endoluminal tracheal occlusion', 'description': 'fetoscopic balloon occlusion at 27 to 29+6 weeks of gestation', 'interventionNames': ['Procedure: fetal endoluminal tracheal occlusion']}], 'interventions': [{'name': 'fetal endoluminal tracheal occlusion', 'type': 'PROCEDURE', 'otherNames': ['Balt Goldbal 2 balloon'], 'description': 'percutaneous fetoscopy, positioning of endoluminal balloon at 27-30 weeks and whenever possible elective removal at 34 weeks', 'armGroupLabels': ['fetal endoluminal tracheal occlusion']}, {'name': 'watchful waiting during pregnancy', 'type': 'OTHER', 'description': 'pregnancy surveillance for fetal wellbeing, development of polyhydramnios and cervical shortening', 'armGroupLabels': ['expectant management during pregnancy']}]}, 'contactsLocationsModule': {'locations': [{'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'University of Texas Health Science Center', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '4101', 'city': 'Brisbane', 'state': 'Queensland', 'country': 'Australia', 'facility': "Mater Mother's Hospital", 'geoPoint': {'lat': -27.46794, 'lon': 153.02809}}, {'zip': '3000', 'city': 'Leuven', 'country': 'Belgium', 'facility': 'University Hospitals Leuven', 'geoPoint': {'lat': 50.87959, 'lon': 4.70093}}, {'zip': 'M5G 1X5', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Mount Sinai Hospital', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': '92141', 'city': 'Clamart', 'country': 'France', 'facility': 'Hôpital Antoine Béclère', 'geoPoint': {'lat': 48.80299, 'lon': 2.26692}}, {'zip': '53105', 'city': 'Bonn', 'country': 'Germany', 'facility': 'University Hospital of Bonn', 'geoPoint': {'lat': 50.73438, 'lon': 7.09549}}, {'zip': '20122', 'city': 'Milan', 'country': 'Italy', 'facility': 'Ospedale Maggiore Policlinico', 'geoPoint': {'lat': 42.78235, 'lon': 12.59836}}, {'zip': '00123', 'city': 'Rome', 'country': 'Italy', 'facility': 'Ospedale Pediatrico Bambino Gesù', 'geoPoint': {'lat': 41.89193, 'lon': 12.51133}}, {'zip': '157-8535', 'city': 'Tokyo', 'country': 'Japan', 'facility': 'National Center for Child Health and Development', 'geoPoint': {'lat': 35.6895, 'lon': 139.69171}}, {'city': 'Warsaw', 'country': 'Poland', 'facility': '1st Department of Obstetrics and Gynecology, Medical University of Warsaw', 'geoPoint': {'lat': 52.22977, 'lon': 21.01178}}, {'zip': '08028', 'city': 'Barcelona', 'state': 'Catalonia', 'country': 'Spain', 'facility': 'Hospital Clinic Barcelona', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'zip': 'SE5 9RS', 'city': 'London', 'country': 'United Kingdom', 'facility': "King's College Hospital", 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'overallOfficials': [{'name': 'Jan Deprest, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Universitaire Ziekenhuizen KU Leuven'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Gasthuisberg', 'class': 'OTHER'}, 'collaborators': [{'name': "King's College Hospital NHS Trust (UK)", 'class': 'UNKNOWN'}, {'name': 'Hospital Clinic of Barcelona', 'class': 'OTHER'}, {'name': 'Hopital Antoine Beclere', 'class': 'OTHER'}, {'name': 'University Hospital, Bonn', 'class': 'OTHER'}, {'name': "Mater Mothers' Hospital", 'class': 'OTHER'}, {'name': "Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico", 'class': 'OTHER'}, {'name': 'Ospedale Pediatrico Bambino Gesù, Rome (IT)', 'class': 'UNKNOWN'}, {'name': 'Mount Sinai Hospital, Canada', 'class': 'OTHER'}, {'name': 'National Center for Child Health and Development, Tokyo (JP)', 'class': 'UNKNOWN'}, {'name': 'The University of Texas Health Science Center, Houston', 'class': 'OTHER'}, {'name': 'Medical University of Warsaw', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD, PhD', 'investigatorFullName': 'Jan Deprest', 'investigatorAffiliation': 'University Hospital, Gasthuisberg'}}}}