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Trial record 19 of 27 for:    Recruiting, Not yet recruiting, Available Studies | "Hernia, Diaphragmatic"

'TOTAL' (Tracheal Occlusion To Accelerate Lung Growth) Trial (TOTAL)

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ClinicalTrials.gov Identifier: NCT02875860
Recruitment Status : Recruiting
First Posted : August 23, 2016
Last Update Posted : January 29, 2018
Sponsor:
Collaborators:
Baylor College of Medicine
Texas Children's Hospital
Universitare Ziekenhuizen Leuven
Information provided by (Responsible Party):
Michael Belfort, Baylor College of Medicine

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.

Condition or disease Intervention/treatment Phase
Hernia Hernia, Diaphragmatic Hernia, DIaphragmatic, Congenital Pathological Conditions, Anatomical Congenital Abnormalities Congenital Diaphragmatic Hernia Fetal Anomaly Fetal Surgery Pulmonary Hypoplasia Device: GoldBal2 detachable balloon Device: Baltaccidbpe100 Delivery Catheter Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : January 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
No Intervention: Standardized postnatal care (Expectant)
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.
Experimental: Prenatal Intervention (FETO)
Patients will undergo fetoscopic endoluminal tracheal occlusion and ideally prenatal reversal of the occlusion followed by standardized postnatal care as in the expectant . In this study FETO (where GoldBal2 detachable balloon and Baltaccidbpe100 Delivery Catheter are used) 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.
Device: GoldBal2 detachable balloon
Placement of the balloon using the plug/unplug method.
Device: Baltaccidbpe100 Delivery Catheter
The catheter assists with implanting the balloon in the plug/unplug method.



Primary Outcome Measures :
  1. Proportion of neonate survival [ Time Frame: At hospital discharge, average 4 months. ]
  2. Participants' supplemental oxygen dependency [ Time Frame: At 6 months of age ]
    Measured as FiO2 amount as a grade (0-III)


Secondary Outcome Measures :
  1. Oxygen dependency [ Time Frame: Measured in baby clinical evaluation at delivery, 1 year, and 2 years old. ]
    Measured as FiO2 amount as a grade (0-III)

  2. CDH defect size [ Time Frame: Measured in neonate at delivery by MRI and/or ultrasound ]
    Postnatal grade classification (A-D) using CDH study group standardized system.

  3. Occurrence of severe pulmonary hypertension [ Time Frame: After delivery ]
    Measured by presence in neonate by ultrasound

  4. ECMO (extracorporeal membrane oxygenation) support [ Time Frame: Measured in baby clinical evaluation at delivery, 6 months, 1 year, and 2 years old ]
    As measured by need (yes/no)

  5. Neonatal intensive care unit use [ Time Frame: Measured in baby clinical evaluation at delivery, 6 months, 1 year, and 2 years old ]
    As measured by days

  6. Ventilator support [ Time Frame: Measured in baby clinical evaluation at delivery, 6 months, 1 year, and 2 years old ]
    As measured by days

  7. Periventricular leukomalacia [ Time Frame: Measured in baby clinical evaluation after delivery at 6 months ]
    As measured by presence in medical record ≤ 2 months postnatally by ultrasound (yes/no)

  8. Neonatal sepsis [ Time Frame: Measured in baby clinical evaluation at delivery, 6 months, 1 year, and 2 years old ]
    As measured by presence in medical record (yes/no)

  9. Intraventricular hemorrhage [ Time Frame: Measured as presence in neonate during first month by MRI and/or ultrasound ]
    Postnatal grade classification (0-III) using standardized system (yes/no)

  10. Retinopathy of prematurity [ Time Frame: Measured in baby clinical evaluation at delivery, 6 months, 1 year, and 2 years old ]
    Postnatal grade classification presence of grade III or higher using standardized system (yes/no)

  11. Full enteral feeding [ Time Frame: Measured in baby clinical evaluation at delivery, 6 months, 1 year, and 2 years old ]
    As measured by number of days until full enteral feeding (if applicable)

  12. Gastroesophageal reflux [ Time Frame: Measured in baby clinical evaluation at delivery, 6 months, 1 year, and 2 years old ]
    Presence of reflux above 1/3 of esophagus on clinically indicated radiologic exam (yes/no)

  13. CDH (Congenital Diaphragmatic Hernia) surgery repair [ Time Frame: Measured in baby clinical evaluation at 6 months ]
    As measured by day of surgery in medical record and use of patch (yes/no)

  14. Survival [ Time Frame: As measured up to 2 years of age ]
    Measured by death (yes/no) and date


Other Outcome Measures:
  1. Pulmonary function [ Time Frame: Measured at up to 4 weeks 6 days prenatally, discharge, and at 1 year of age ]
    Measured by ultrasound and/or MRI as % o/e LHR = (Observed LHR/ Expected LHR) Lung to Head Ratio

  2. Lung volume [ Time Frame: Measured at up to 4 weeks 6 days prenatally, discharge, and at 1 year of age ]
    Measured by 2D ultrasound and/or fetal MRI as % o/e TLV = (Observed TLV/ Expected TLV) Total Lung Volume

  3. Prenatal liver position [ Time Frame: Up to 4 weeks 6 days prenatally. ]
    In case of liver herniation, measured by ultrasound and/or MRI as liver-to-thorax volume (LiTR)

  4. Neurodevelopmental milestones [ Time Frame: Measured at discharge, 12 months and 2 years of age. ]
    Using validated questionnaire: Ages and Stages (http://agesandstages.com/)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02875860


Contacts
Contact: Michael Belfort, MD, PhD 832-826-7375 belfort@bcm.edu
Contact: Wyoniquea D Rahming, MBA 832-826-7345 rahming@bcm.edu

Locations
United States, Texas
Baylor College of Medicine/Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Michael Belfort, MD, PhD    832-826-7375    belfort@bcm.edu   
Contact: Wyoniquea D Rahming, MBA    832-826-7345    rahming@bcm.edu   
Principal Investigator: Michael Belfort, MD, PhD         
Sub-Investigator: Oluyinka Olutoye, MD,PhD         
Sponsors and Collaborators
Michael Belfort
Baylor College of Medicine
Texas Children's Hospital
Universitare Ziekenhuizen Leuven
Investigators
Principal Investigator: Michael Belfort, MD, PhD Baylor College of Medicine/Texas Children's Hospital

Additional Information:
Publications:
Jani J, Nicolaides K, Gratacos E, et al. 558: Short term neonatal morbidity in severe left-sided congenital diaphragmatic hernia treated by tracheal occlusion before 30 weeks. Am J Obstet Gynecol Dec;197(6),Supplement:S162.
Jani J, Benachi A, Mitanchez D, et al. 2006. Lung-to-head ratio and liver position to predict neonatal morbidity in fetuses with isolated congenital diaphragmatic hernia: A multicenter study. Am Journal Obstet Gynecol 195(6); Supplement:S60.

Responsible Party: Michael Belfort, Principal Investigator, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02875860     History of Changes
Other Study ID Numbers: H-39398
First Posted: August 23, 2016    Key Record Dates
Last Update Posted: January 29, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Our study is part of a multi-center study, led by Universitare Ziekenhuizen Leuven, Study Chair: Jan A. Deprest, MD PhD; NCT00763737. Transmission of data to collaborators will occur over secure and encrypted email and SSL web portals. Personal Health Information (PHI) will not be reused or disclosed to (shared with) any other person or entity, except as required by law, for authorized oversight of the research study, or for other research for which the use or disclosure of the PHI would be permitted under the Privacy Rule. Randomization will be done via a purpose-designed website, hosted by the lead site. Data of individual patients will be accessible via the website to the treating physicians. Only the central data manager and statistician have general overview of the data. Data gathered won't be disclosed prior to closure and reporting of this study, in order not to compromise recruitment and unbiased conduction of the trial. By participating in this study, partners agree to this.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Michael Belfort, Baylor College of Medicine:
CDH
Congenital Diaphragmatic Hernia
Fetal Tracheal Occlusion
FETO
plug-unplug
GoldBal2
Balloon
Goldvalve Balloon
TOTAL

Additional relevant MeSH terms:
Hernia
Hernia, Diaphragmatic
Hernias, Diaphragmatic, Congenital
Congenital Abnormalities
Pathological Conditions, Anatomical