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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01240057




Registration number
NCT01240057
Ethics application status
Date submitted
4/08/2010
Date registered
15/11/2010
Date last updated
11/03/2020

Titles & IDs
Public title
Tracheal Occlusion To Accelerate Lung Growth (TOTAL) Trial for Severe Pulmonary Hypoplasia
Scientific 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.
Secondary ID [1] 0 0
B32220108118
Secondary ID [2] 0 0
ML 6277
Universal Trial Number (UTN)
Trial acronym
TOTAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Congenital Diseases 0 0
Diaphragmatic Hernia 0 0
Pulmonary Hypoplasia 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - fetal endoluminal tracheal occlusion
Other interventions - watchful waiting during pregnancy

Placebo Comparator: expectant management during pregnancy - watchful waiting during pregnancy

Experimental: fetal endoluminal tracheal occlusion - fetoscopic balloon occlusion at 27 to 30 weeks of gestation


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

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

Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
at discharge from neonatal intensive care unit
Secondary outcome [1] 0 0
prenatal increase in lung volume - volume of lung after occlusion
Timepoint [1] 0 0
2 weeks
Secondary outcome [2] 0 0
grading of oxygen dependency
Timepoint [2] 0 0
56 days of life
Secondary outcome [3] 0 0
occurrence of pulmonary hypertension - determined by cardiac ultrasound
Timepoint [3] 0 0
within first weeks of life
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
within hospital stay
Secondary outcome [5] 0 0
number of days on ventilator
Timepoint [5] 0 0
within NICU stay
Secondary outcome [6] 0 0
presence of periventricular leucomalacia
Timepoint [6] 0 0
2 months of life
Secondary outcome [7] 0 0
presence of neonatal sepsis, intraventricular haemorrhage, retinopathy grade III or higher
Timepoint [7] 0 0
within hospital stay
Secondary outcome [8] 0 0
number of days till full enteral feeding
Timepoint [8] 0 0
within first 2 years of life
Secondary outcome [9] 0 0
presence of gastro-esophagal reflux
Timepoint [9] 0 0
at discharge
Secondary outcome [10] 0 0
day of surgery
Timepoint [10] 0 0
within hospital stay
Secondary outcome [11] 0 0
requirement for use of patch for repair
Timepoint [11] 0 0
at the time of surgery
Secondary outcome [12] 0 0
neurodevelopment at 12 and 24 months
Timepoint [12] 0 0
24 months
Secondary outcome [13] 0 0
pulmonary function at one year of age
Timepoint [13] 0 0
one year of age

Eligibility
Key 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
Minimum age
18 Years
Maximum age
50 Years
Gender
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Mater Mother's Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
Belgium
State/province [2] 0 0
Leuven
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
France
State/province [4] 0 0
Clamart
Country [5] 0 0
Germany
State/province [5] 0 0
Bonn
Country [6] 0 0
Italy
State/province [6] 0 0
Milano
Country [7] 0 0
Italy
State/province [7] 0 0
Rome
Country [8] 0 0
Japan
State/province [8] 0 0
Tokyo
Country [9] 0 0
Poland
State/province [9] 0 0
Warsaw
Country [10] 0 0
Spain
State/province [10] 0 0
Catalunya
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
University Hospital, Gasthuisberg
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
King's College Hospital NHS Trust (UK)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Hospital Clinic of Barcelona
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Hopital Antoine Beclere
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University Hospital, Bonn
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Mater Mothers' Hospital
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Ospedale Maggiore Policlinico, Milan (IT)
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Ospedale Pediatrico Bambino Gesù, Rome (IT)
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Mount Sinai Hospital, Canada
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
National Center for Child Health and Development, Tokyo (JP)
Address [9] 0 0
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
University of Texas Health Science Center at Houston, TX (US)
Address [10] 0 0
Country [10] 0 0
Other collaborator category [11] 0 0
Other
Name [11] 0 0
1st Department of Obstetrics and Gynecology, Medical University of Warsaw
Address [11] 0 0
Country [11] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01240057
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Jan Deprest, MD
Address 0 0
Universitaire Ziekenhuizen Leuven
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications