Clinical trial NCT02875860: 'TOTAL' (Tracheal Occlusion To Accelerate Lung Growth) Trial
Official title: TOTAL TRIAL: Randomized Trial of Fetoscopic Endoluminal Tracheal Occlusion (FETO) Versus Expectant Management During Pregnancy in Fetuses With Left-Sided and Isolated Congenital Diaphragmatic Hernia and Moderate Pulmonary Hypoplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hernia
Hernia, Diaphragmatic
Hernia, DIaphragmatic, Congenital
Pathological Conditions, Anatomical
Congenital Abnormalities
Congenital Diaphragmatic Hernia
Fetal Anomaly
Fetal Surgery
Pulmonary Hypoplasia
Keywords: CDH
Congenital Diaphragmatic Hernia
Fetal Tracheal Occlusion
FETO
plug-unplug
GoldBal2
Balloon
Goldvalve Balloon
TOTAL
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Baylor College of Medicine
name: Universitaire Ziekenhuizen KU Leuven
First posted: 2016-08-23
Enrollment: 5
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will test whether temporary fetoscopic endoluminal tracheal occlusion (FETO) rather than expectant management during pregnancy, followed by standardized postnatal management, increases survival at discharge and decreases oxygen need at 6 months in case of survival till discharge.

Detailed description: This is a multi-center, non-blinded randomized controlled trial in fetuses with isolated moderate CDH, i.e. moderate lung hypoplasia (as determined by prenatal assessment of lung development). It essentially compares fetal therapy added to conventional postnatal care, versus expectant prenatal management during pregnancy followed by conventional postnatal care.

Enrollment:

Following completion of an inclusion/exclusion criteria checklist and obtaining informed consent, the subject will be randomized into two groups ("FETO" and "expectant").

Procedures:

Group I: Standardized postnatal care (expectant group): mothers will be expectantly managed during pregnancies and babies receive standardized postnatal care at a tertiary center used to manage babies with CDH. The recommendation is that they adhere to consensus guidelines published on the study website.

Group II: Prenatal intervention (FETO group): patients will undergo fetoscopic tracheal occlusion and ideally prenatal reversal of the occlusion followed by standardized postnatal care as in I. In this study FETO is to be done between 30 weeks plus 0 day and 31 weeks plus 6 days and removal of the balloon at 34 weeks plus 0 day to 34 weeks plus 6 days.

This study trial is a pragmatical or efficacy trial: ideally mothers will deliver after removal of the balloon at those tertiary centers, typically offering postnatal care for the patient involved. In group II (FETO-group), mothers will, in between placement and removal of the balloon, thus carrying a fetus with obstructed airways, ideally remain under the care of our local fetal treatment center (further referred to as FETO center). As many as possible precautions are taken to avoid problems with balloon removal in case of earlier than expected delivery.

* Balloons are to be electively removed prior to 35 weeks. FETO centers will provide 24/24 hours and 7/7 days services for management of fetuses with obstructed airways, either in utero or during labor and delivery.
* Patients in the study and randomized to FETO, will be encouraged to stay near the FETO center. After reversal of the occlusion the patient will be referred to the tertiary care center where delivery and postnatal care will be undertaken. If the patient is not remaining at or close to the FETO center, the postnatal treatment center should organize likewise EXIT services.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18 years or more, who are able to consent,
2. Singleton pregnancy,
3. Chromosomally normal fetus,
4. Gestation at randomization prior to 31 weeks plus 5 days or so that occlusion is done at the latest on 31 weeks plus 6 days,
5. Fetus is estimated to have moderate pulmonary hypoplasia, defined prenatally as:

   • O/E LHR 25-34.9% (included; irrespective of the position of the liver) • O/E LHR 35-44.9% (included) with intrathoracic liver herniation as determined by ultrasound or MRI.

   The O/E LHR will be determined by the FETO centers as follows:
   * Measurement of the contralateral lung area preferentially by the tracing method at the 4-chamber view of the heart; if by other method adjusted normative ranges must be used.
   * Measurement of the head circumference at the standard biparietal view of the head
   * The observed lung area: calculation of the LHR as the ratio of the measurements of the lung area to head circumference
   * The expected lung area is the lung area of a normal gestational age match, as determined by the head circumference of the index case in a normogram established for the same measurement method (tracing method in this case). A calculator for this will be available on the website of the study.
   * Calculation of the observed over expected lung area,
6. Acceptance of randomization and the consequences for the further management during pregnancy and thereafter, this includes the required observation following FETO surgery, which lasts up to 4 weeks after balloon is in place,
7. 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," and
8. Provide written consent to participate.
9. Fetus with no major anomalies that would impact the clinical course or outcomes.

Exclusion Criteria:

1. Maternal contraindication to fetoscopic surgery or severe medical condition in pregnancy that make fetal intervention risky,
2. Technical limitations precluding fetoscopic surgery, such as severe maternal obesity, uterine fibroids or potentially others, not anticipated at the time of writing this protocol,
3. Preterm labor, cervix shortened (\<15 mm at randomization) or uterine anomaly strongly predisposing to preterm labor, placenta previa,
4. Patient age less than 18 years,
5. Psychosocial ineligibility, precluding consent,
6. Diaphragmatic hernia: right-sided or bilateral, major anomalies, isolated left-sided outside the O/E LHR limits for the inclusion criteria, and
7. Patient refusing randomization, to comply with required 4-week observation after balloon placement, or to comply with return to FETO center during the time period the airways are occluded or for elective removal of the balloon.
8. Patient allergic to latex.

Primary outcomes:
measure: Proportion of Neonate Survival at Discharge From Hospital
timeFrame: At hospital discharge, an average of 1.5 months
measure: Participants Requiring Supplemental Oxygen
timeFrame: At 6 months of age
Secondary outcomes:
measure: Grade of Oxygen Dependency
timeFrame: at 6 months of age
measure: Occurrence of Severe Pulmonary Hypertension
timeFrame: During the first 4 weeks of life (neonatal period).
measure: ECMO (Extracorporeal Membrane Oxygenation) Support
timeFrame: Neonatal period (during the first 4 weeks of life)
measure: CDH Defect Size
timeFrame: Measured in neonate at delivery by MRI and/or ultrasound
measure: Number of Days in the NICU
timeFrame: At the time of discharge from the NICU, an average of 1.5 months
measure: Ventilatory Support
timeFrame: During the first 4 weeks of life (neonatal period)
measure: Number of Subjects With Periventricular Leukomalacia (PVL)
timeFrame: During first 2 months of life
measure: Neonatal Sepsis
timeFrame: During the first 4 weeks of life (neonatal period)
measure: Intraventricular Hemorrhage
timeFrame: During first month of life
measure: Retinopathy of Prematurity
timeFrame: At the time of discharge from the NICU, an average of 1.5 months
measure: Days to Full Enteral Feeding
timeFrame: At hospital discharge, an average of 1.5 months
measure: Gastroesophageal Reflux
timeFrame: At the time of discharge from the NICU, an average of 1.5 months
measure: CDH (Congenital Diaphragmatic Hernia) Surgery Repair
timeFrame: From the time of birth until discharge from the NICU
measure: Use of Patch in CDH Repair
timeFrame: At the time of the surgical repair postnatally, up to 3 days postnatal
measure: Survival
timeFrame: At 24 months of age
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine/Texas Children's Hospital
state: Texas
Study officials:
affiliation: Baylor College of Medicine - Texas Children's Hospital
name: Michael Belfort, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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