Smart Removal for Congenital Diaphragmatic Hernia (SmartRemoval)
Primary Purpose
Congenital Diaphragmatic Hernia
Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Fetoscopic Endoluminal Tracheal Occlusion with the Smart-TO Balloon
Sponsored by
About this trial
This is an interventional treatment trial for Congenital Diaphragmatic Hernia
Eligibility Criteria
Inclusion Criteria:
Women carrying a fetus with isolated CDH eligible for FETO, i.e. with severe or moderate hypoplasia:
- Left sided CDH with severe (i.e. quotient of observed-to-expected- lung-to-head ratio under 25%) or moderate pulmonary hypoplasia (observed-to-expected- lung-to-head ratios of 25 to 34.9% (any liver position), or 35 to 44.9% with intrathoracic liver herniation)
- Right sided CDH with severe pulmonary hypoplasia (quotient of observed-to-expected- lung-to-head ratio under 50%)
- Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
- Maternal age of 18 years or older
- Single pregnancy
- Signed informed consent
- Consent to have an ultrasound of the uterus after delivery when indicated
- Postnatal management center agrees to participate
Exclusion Criteria:
Participants eligible for this Trial must not meet any of the following criteria:
- History of allergy to latex
- Contraindication to fetoscopy and FETO (maternal diseases or technical limitations making prenatal surgery hazardous or impossible)
- Premature Membrane Rupture (PROM)
- Multiple pregnancy
- Maternal age less than 18 years
- Refusal to stay close to the UZ Leuven until balloon removal
- Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol
- Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial
- Participation in another interventional trial with an investigational medicinal product (IMP) or device
Sites / Locations
- UZ LeuvenRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Procedure FETO with the Smart-TO balloon
Arm Description
Fetal endoscopic tracheal occlusion using the Smart-TO balloon. Balloon removal procedure by peripheral course around the MR scanner
Outcomes
Primary Outcome Measures
To demonstrate the ability to prenatally deflate the Smart-TO balloon by the magnetic fringe field generated by an MRI scanner
• Deflation rate after MRI exposure, assessed through ultrasound (US) immediately after MRI exposure
Secondary Outcome Measures
Balloon expulsion from the fetal airways after deflation.
Absence of balloon visualization with ultrasound
Rate of spontaneous deflation of the balloon.
• Spontaneous balloon deflation prior to MRI exposure, as diagnosed through ultrasound. Although a rare event, this has been reported with the standard Goldbal2® balloon in 3.1%
Percentage of lung growth
• Lung growth assessed by US prior to deflation, measured by change in the observed-to-expected lung-to-head-ratio (o/e LHR) before balloon insertion and two weeks after FETO
Number of adverse events related to the balloon.
Balloon localisation at birth
• Localisation of the balloon either by (1) direct visualization within the amniotic fluid, membranes or placenta, (2) postnatal chest X-ray of the newborn, and (3) ultrasound of the postpartum uterus
Full Information
NCT ID
NCT05100693
First Posted
September 20, 2021
Last Updated
October 19, 2021
Sponsor
Universitaire Ziekenhuizen KU Leuven
1. Study Identification
Unique Protocol Identification Number
NCT05100693
Brief Title
Smart Removal for Congenital Diaphragmatic Hernia
Acronym
SmartRemoval
Official Title
Non-invasive Removal of the Smart Tracheal Occlusion Device for Fetal Congenital Diaphragmatic Hernia: A Feasibility Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 8, 2021 (Actual)
Primary Completion Date
August 1, 2026 (Anticipated)
Study Completion Date
November 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to demonstrate the ability to prenatally deflate and to evaluate the safety of the Smart-TO device for fetoscopic endoluminal tracheal occlusion (FETO) in fetuses with congenital diaphragmatic hernia and moderate to severe pulmonary hypoplasia.
Detailed Description
Congenital diaphragmatic hernia (CDH) is a birth defect characterized by impaired closure of the diaphragm. This enables abdominal viscera to herniate into the thoracic cavity, leading to hypoplastic lungs and impaired lung vasculature. Fetal lung growth may be stimulated by Fetoscopic Endoluminal Tracheal Occlusion (FETO). For left-sided CDH, there is now level I evidence that it significantly improves survival in severe cases; the effect in moderate cases is much less.
Despite its benefits, the current procedure has many disadvantages. First, there is the need for prenatal reversal of the balloon, which is invasive. In utero balloon removal re-establishes airway patency. This can be done electively at 34 weeks or earlier if required, but preferentially at least 24 hours before birth. "Unplugging" requires a second procedure and a specialist team familiar with the procedure, which is available at all times. In the most extensive series published thus far, 28% of balloon removals were in an emergency setting. The only neonatal deaths were caused by complications when balloon reversal was attempted in centers without experience or unprepared. In utero reversal of the occlusion is also an invasive procedure because it requires ultrasound-guided puncture or fetoscopy. The second procedure adds both to the fetal and maternal risks.
Balloon removal is a difficult procedure that needs expertise.
Prenatal balloon removal procedure can fail in 3.4% even in experienced centers.
Balloon removal is not feasible in utero in 12.6 to 24.7% of the cases.
Balloon removal is performed in an emergency setting in 28% of the cases.
Balloon removal can lead to neonatal death in none well-trained centers.
In utero balloon removal may induce delivery within one week in 25% of cases.
Patients are requested to stay close to a FETO center for the entire duration of the tracheal occlusion, which is a burden on the family, limiting the acceptability of FETO.
The Smart-TO balloon allows remotely controlled non-invasive reversal of the occlusion. Around the balloon neck, there is a metallic cylinder and inside a magnetic ball, which acts as a valve. Deflation occurs under a strong magnetic field, as generated by a clinical MRI machine. For that, it is sufficient for the pregnant woman to walk around a clinical MRI machine. The opening of the valve induces the deflation of the balloon, which is then washed out by the fluid coming out from the lungs.
The investigators have completed the translational research that proved the safety and efficacy of this balloon for FETO and want to use this medical device for the first time in humans. The purpose of this first in-woman study is to demonstrate the ability to prenatally deflate and to evaluate the safety of the Smart-TO device for FETO in fetuses with congenital diaphragmatic hernia and moderate to severe pulmonary hypoplasia. Secondary outcomes include safety parameters.
FETO with Smart-TO balloon will be performed between 27 and 31wks + 6 days depending on the severity of pulmonary hypoplasia, according to the same technique used with the balloon usually used for the FETO procedure. Reversal of the tracheal occlusion will be performed between 34 and 34wks + 6 days or earlier if necessary. In the unlikely event of a patient with imminent signs of delivery, balloon removal will be done on placental circulation or postnatally. This will ensure the patient's safety. The patient will be asked to walk around the MR scanner to open the magnetic valve and induce the deflation of the balloon. Afterwards, an ultrasound will be performed by two experienced sonographers to assess balloon deflation. In the case of deflation failure, a second and -if necessary- a third MRI exposure will be attempted following ultrasound confirmation to ensure balloon deflation. In the case of balloon failure to deflate or any doubt about deflation, an MRI with image acquisition will be performed to (1) attempt deflation and (2) assess the airway patency. In the case of failure to deflate, balloon removal will be done by fetoscopy, placental circulation, or postnatally (depending on the clinical scenario). Within 24 hours after balloon deflation:
An MRI (with image acquisition) will be performed to locate the deflated balloon and as a second safety measure to ensure the patency of the airways.
The patient will be allowed to return to her tertiary centre of preference once the airways' patency is confirmed.
Delivery does not differ from the standard care protocol for children with CDH. In the case of MRI deflation protocol, the following will be done to locate the balloon:
Inspection and search of any amniotic fluid, membranes, and the placenta*
Standard X-ray of the newborn, which is standard, to assess lungs, airways, intubation, and location of the stomach and nasogastric tube; on that the balloon may be visible, e.g., in the stomach.
An ultrasound of the postpartum uterus will be done to demonstrate that the uterine cavity is empty.
The follow-up and management of the newborn will be according to the standardized management protocol of the CDH EURO Consortium. Data collection will be stopped at the moment the child is discharged from the hospital.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Diaphragmatic Hernia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Procedure FETO with the Smart-TO balloon
Arm Type
Experimental
Arm Description
Fetal endoscopic tracheal occlusion using the Smart-TO balloon. Balloon removal procedure by peripheral course around the MR scanner
Intervention Type
Other
Intervention Name(s)
Fetoscopic Endoluminal Tracheal Occlusion with the Smart-TO Balloon
Other Intervention Name(s)
FETO
Intervention Description
Fetal Endoscopic Tracheal Occlusion using the Smart-TO balloon and non-invasive balloon removal by the peripheral magnetic field of an magnetic resonance scanner.
Primary Outcome Measure Information:
Title
To demonstrate the ability to prenatally deflate the Smart-TO balloon by the magnetic fringe field generated by an MRI scanner
Description
• Deflation rate after MRI exposure, assessed through ultrasound (US) immediately after MRI exposure
Time Frame
Up to 34+6 weeks of pregnancy
Secondary Outcome Measure Information:
Title
Balloon expulsion from the fetal airways after deflation.
Description
Absence of balloon visualization with ultrasound
Time Frame
Immediately after MRI exposure
Title
Rate of spontaneous deflation of the balloon.
Description
• Spontaneous balloon deflation prior to MRI exposure, as diagnosed through ultrasound. Although a rare event, this has been reported with the standard Goldbal2® balloon in 3.1%
Time Frame
Up to 34+6 weeks of pregnancy
Title
Percentage of lung growth
Description
• Lung growth assessed by US prior to deflation, measured by change in the observed-to-expected lung-to-head-ratio (o/e LHR) before balloon insertion and two weeks after FETO
Time Frame
Two weeks after FETO
Title
Number of adverse events related to the balloon.
Time Frame
From date of inclusion until date of discharge from the hospital
Title
Balloon localisation at birth
Description
• Localisation of the balloon either by (1) direct visualization within the amniotic fluid, membranes or placenta, (2) postnatal chest X-ray of the newborn, and (3) ultrasound of the postpartum uterus
Time Frame
At birth
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women carrying a fetus with isolated CDH eligible for FETO, i.e. with severe or moderate hypoplasia:
Left sided CDH with severe (i.e. quotient of observed-to-expected- lung-to-head ratio under 25%) or moderate pulmonary hypoplasia (observed-to-expected- lung-to-head ratios of 25 to 34.9% (any liver position), or 35 to 44.9% with intrathoracic liver herniation)
Right sided CDH with severe pulmonary hypoplasia (quotient of observed-to-expected- lung-to-head ratio under 50%)
Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
Maternal age of 18 years or older
Single pregnancy
Signed informed consent
Consent to have an ultrasound of the uterus after delivery when indicated
Postnatal management center agrees to participate
Exclusion Criteria:
Participants eligible for this Trial must not meet any of the following criteria:
History of allergy to latex
Contraindication to fetoscopy and FETO (maternal diseases or technical limitations making prenatal surgery hazardous or impossible)
Premature Membrane Rupture (PROM)
Multiple pregnancy
Maternal age less than 18 years
Refusal to stay close to the UZ Leuven until balloon removal
Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol
Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial
Participation in another interventional trial with an investigational medicinal product (IMP) or device
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jan Depret, PhD, MD
Phone
+3216345123
Email
jan.deprest@uzleuven.be
First Name & Middle Initial & Last Name or Official Title & Degree
David Basurto, MD
Phone
+3216341974
Email
david.basurto@uzleuven.be
Facility Information:
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Deprest, MD, PhD
Phone
+3216345123
Email
jan.deprest@uzleuven.be
First Name & Middle Initial & Last Name & Degree
Francesca Russo, MD, PhD
Phone
+3216340829
Email
francesca.russo@uzleuven.be
12. IPD Sharing Statement
Plan to Share IPD
No
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Smart Removal for Congenital Diaphragmatic Hernia
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