Prenatal Endoscopic Repair of Fetal Spina Bifida (ENDOSPIN)

The purpose of this study is to determine the feasibility of prenatal minimally-invasive fetoscopic closure with i) uterine exteriorization for a minimally-invasive repair under amniotic carbon dioxide insufflation ii) two trocars for the dissection and the cover with one patch or the suture of the skin edges by stitch

Study Overview

• Status: Completed
• Conditions: Myelomeningocele
• Intervention / Treatment: Procedure: endoscopic repair of myelomeningocele before 26 SA

Detailed Description

Compared with an open approach involving laparotomy and hysterotomy, an endoscopic approach for the prenatal surgery of myelomeningocele offers at least two potential advantages: i) it may reduce the maternal and obstetric morbidity related to the hysterotomy; ii) it may be performed earlier in gestation than open surgery, therefore potentially further reducing exposition of the spinal chord to the intraamniotic environment and thus improving the overall prognosis of the malformation. This study aims to evaluate the feasibility and potential benefits of a minimally invasive endoscopic procedure for the prenatal treatment of myelomeningocele in a single-center trial.

Technically the procedure will be performed through 2 intra-amniotic ports, under fetoscopic visualization and intra-amniotic carbon dioxide insufflation. The defect will be dissected and the cord replaced in the canal. Closure will be performed by suturing paravertebral muscles using a barbed running suture. A Duragen patch will be sutured when primary closure is deemed impossible.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Necker Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient > 18 years old, with an assumption by health insurance, understanding and speaking French
• A term < or = 26 +0 weeks gestational age
• Single-Pregnancy
• Myelomeningocele with higher-level defect between S1 and T1
• Arnold Chiari anomaly
• No associated anomaly or chromosic anomaly

Exclusion Criteria:

• severe foetal kyphoscoliosis associated
• Increased risk of preterm birth: cervical length <15 mm, history of at least 2 late miscarriages, existing premature rupture of membrane
• placenta previa, accreta or placental abruption
• Maternal obesity with BMI> 35
• Uterine anomalies : large interstitial uterine fibroid, uterine malformation
• maternal infection with a foetal transmission risk: HIV, HBV, HCV
• Maternal contradiction in surgery or anesthesia
• poor social status and/or social isolation
• impossible post-surgery follow-up
• want to have a medical pregnancy termination

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Minimally-invasive endoscopic repair; endoscopic repair of myelomeningocele before 26 SA	Procedure: endoscopic repair of myelomeningocele before 26 SA; prenatal minimally-invasive fetoscopic closure with iii) uterine exteriorization for a minimally-invasive repair under amniotic carbon dioxide insufflation iv) two trocars for the dissection and the cover with one patch or the suture of the skin edges by stitch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful surgery	Composite criteria: dissection of the placode; primary coverage or use of a patch; using only endoscopy with two trocars	Before 26 gestational weeks
Neonatal surgery	Need for neonatal surgery	Day 0 (birth of neonates)
Arnold Chiari anomaly at birth	the existence of an Arnold Chiari anomaly at birth	Day 0 (birth of neonates)
Ventriculo-peritoneal shunt	Ventriculo-peritoneal shunt within the 6 months after birth	Within the 6 months after birth
Level of injury		Within the 6 months after birth
Foetal morbidity	Composite criteria: Stillbirth; Premature Rupture of Membranes; Preterm birth; Chorioamnionitis; Hemorrhagic complications during the peri-operative period; Other serious adverse events	From surgery to delivery
Motor lower limb improvement outcomes		Within the 6 months after birth
Maternal morbidity	Composite criteria: Stillbirth; Premature Rupture of Membranes; Preterm birth; Chorioamnionitis; Hemorrhagic complications during the peri-operative period; Other serious adverse events	From surgery to delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological development	Composite criteria: Motor deficit medullary reflex orthopedic anomalies consequences on perinea and sphincter	Within the 12 months after birth

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Julien Stirnemann, MD, PhD, Assistance Publique - Hôpitaux de Paris; Principal Investigator: Yves Ville, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Verbeek RJ, Heep A, Maurits NM, Cremer R, Hoving EW, Brouwer OF, van der Hoeven JH, Sival DA. Fetal endoscopic myelomeningocele closure preserves segmental neurological function. Dev Med Child Neurol. 2012 Jan;54(1):15-22. doi: 10.1111/j.1469-8749.2011.04148.x. Epub 2011 Nov 29.
• Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011 Mar 17;364(11):993-1004. doi: 10.1056/NEJMoa1014379. Epub 2011 Feb 9.
• Kohl T. Percutaneous minimally invasive fetoscopic surgery for spina bifida aperta. Part I: surgical technique and perioperative outcome. Ultrasound Obstet Gynecol. 2014 Nov;44(5):515-24. doi: 10.1002/uog.13430.
• Degenhardt J, Schurg R, Winarno A, Oehmke F, Khaleeva A, Kawecki A, Enzensberger C, Tinneberg HR, Faas D, Ehrhardt H, Axt-Fliedner R, Kohl T. Percutaneous minimal-access fetoscopic surgery for spina bifida aperta. Part II: maternal management and outcome. Ultrasound Obstet Gynecol. 2014 Nov;44(5):525-31. doi: 10.1002/uog.13389.
• Arthuis C, James S, Bussieres L, Hovhannisyan S, Corroenne R, Ville Y, Stirnemann JJ. Laparotomy-Assisted 2-Port Fetoscopic Repair of Spina Bifida Aperta: Report of a Single-Center Experience in Paris, France. Fetal Diagn Ther. 2022;49(9-10):377-384. doi: 10.1159/000525552. Epub 2022 Aug 31.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2017
• Primary Completion (Actual): July 6, 2022
• Study Completion (Actual): July 6, 2022

Study Registration Dates

• First Submitted: February 15, 2015
• First Submitted That Met QC Criteria: March 11, 2015
• First Posted (Estimated): March 18, 2015

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: outcome; fetal surgery; Minimally-invasive endoscopic repair; Foetus
• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Nervous System Malformations; Neural Tube Defects; Meningomyelocele; Spina Bifida Cystica; Spinal Dysraphism
• Other Study ID Numbers: P141202; 2014-A01948-39 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No