Fetal Treatment of Galenic Malformations

This is a prospective, single-arm non-randomized interventional study of fetuses to assess the safety and efficacy of fetal embolization of Vein of Galen Malformation (VOGM). Subjects will receive a one-time study intervention of fetal embolization. Follow-up assessments will be collected every 4 weeks until delivery, as per standard of care. After delivery, neurological assessments will be performed every 6 months for 2 years (adjusted for gestational age). Data will be compared to historical cohorts.

Study Overview

• Status: Recruiting
• Conditions: Vein of Galen Malformations
• Intervention / Treatment: Device: Fetal embolization of vein of Galen malformation using Target XL and XXL Detachable Coils

Detailed Description

The study involves a single fetal intervention of maternal transuterine, fetal transcranial torcular puncture and median prosencephalic vein embolization. Detachable platinum coils (Target XL and XXL Detachable Coil, Stryker Neurovascular) will be used to pack the prosencephalic varix. This procedure will take place in an obstetric OR at Brigham and Women's Hospital. Data will be collected every 4 weeks post-procedure until delivery, as per standard of care. Data regarding delivery and post-delivery status will also be collected until the subject is discharged from the hospital. After delivery, neurological assessments will be performed every 6 months for 2 years (adjusted for gestational age). Data will be compared to historical cohorts.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Darren Orbach, MD PhD; Phone Number: 617-355-5012; Email: Darren.Orbach@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Darren Orbach, MD PhD; Phone Number: 617-355-5012; Email: Darren.Orbach@childrens.harvard.edu
      • Principal Investigator: Darren Orbach, MD PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pregnant woman carrying a fetus harboring a vein of Galen malformation in whom the straight sinus or falcine sinus draining the prosencephalic varix measures 7 mm or more on fetal MRI (medio-lateral diameter measured at the narrowest point of the sinus along the rostral-caudal axis, assessed on a T2-weighted coronal slice).
• Fetal gestational age between 23 weeks and term as determined by clinical information and evaluation of first ultrasound.
• Anatomic diagnosis of fetal vein of Galen malformation.
• Well preserved brain parenchyma.
• Maternal age of 18 years and older.
• Eligible for continuous lumbar epidural anesthesia.
• Able to travel to study site for study evaluation, procedures and visits.

Exclusion Criteria:

• Extensive fetal brain parenchymal injury/gliosis, >10% of supratentorial brain volume (i.e., SFP presentation). This is a degree of fetal brain injury beyond which the risk of significant neurological morbidity is high, based on studies of prenatal ischemic stroke.
• Irreversible fetal non-brain organ injury (e.g. hydrops fetalis as a manifestation of heart failure, a finding which portends fatal outcome in fetuses with vein of Galen malformation), i.e., SFP presentation.
• Fetus with VOGM in whom the straight sinus or falcine sinus draining the prosencephalic varix measures less than 8 mm on fetal MRI (T2-weighted coronal slice, medio-lateral diameter measured at the narrowest point of the sinus along the anterior-posterior axis), fitting fetal MRI criteria for likely evolution into the IT cohort.
• Severe maternal obesity pre-pregnancy as defined by body mass index (BMI) of 40 or greater.
• Fetuses with major congenital anomalies.
• Evidence of preterm labor, rupture of membranes or abruption.
• Maternal coagulopathy: INR > 1.2; PT/PTT above normal ranges for the lab; platelets <100.
• Medical disease requiring current anticoagulation including maternal deep vein thrombosis.
• Prior maternal medical history that would preclude epidural anesthesia.
• Multi-fetal pregnancy.
• Placenta previa or accreta.
• Participation in another fetal study that influences maternal and fetal morbidity and mortality.
• Known maternal hypersensitivity to 316LM stainless steel.
• Supine hypotensive syndrome.

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: Fetal embolization of vein of Galen malformation; This is a single-arm study. Fetal subjects will undergo a one-time intervention of fetal embolization of vein of Galen malformation.	Device: Fetal embolization of vein of Galen malformation using Target XL and XXL Detachable Coils; The study involves a single fetal intervention of maternal transuterine, fetal transcranial torcular puncture and median prosencephalic vein embolization. Detachable platinum coils (Target XL and XXL Detachable Coil, Stryker Neurovascular) will be used to pack the prosencephalic varix.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prenatal safety of fetal embolization for patients with vein of Galen malformations	The procedure is deemed safe if; None of the following unacceptable events occur within 7 days of fetal embolization:Fetal deathFetal intracranial hemorrhage, either parenchymal or extra-axial, other than petechial hemorrhage.Maternal death; None of the following unacceptable events occur between fetal embolization and delivery:Intra-procedural and post-procedural morbidity to the fetus and mother, probably related to the fetal intervention, e.g. placental abruption with subsequent sequelaePreterm delivery < 28 weeks, probably related to the fetal interventionMaternal blood transfusion or unanticipated surgical intervention, probably related to the fetal interventionPresence of fetal imaging evidence of new brain injury in a location or pattern unexpected for the natural history of vein of Galen malformation, probably related to the fetal intervention	From fetal embolization to delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of fetal embolization for patients with vein of Galen malformations	The procedure is deemed efficacious if none of the following serious postnatal events occur within 30 days of birth: Urgent neonatal embolization is needed. Without fetal intervention, we'd expect 80% of the cohort to require such intervention.; Neonatal death. Without fetal intervention, we'd expect a mortality rate of 40% in this cohort.; Brain MRI within the first three weeks after birth reveals parenchymal brain injury (acute infarct or gliosis) affecting > 10% of the supratentorial brain volume. Without fetal intervention, we'd expect 30% of patients in this cohort to show this kind of injury.	Within 30 days of birth

Collaborators and Investigators

• Sponsor: Darren Orbach
• Investigators: Principal Investigator: Darren Orbach, MD PhD, Boston Children's Hospital

Publications and helpful links

General Publications

• See AP, Wilkins-Haug LE, Benson CB, Tworetzky W, Orbach DB. Percutaneous transuterine fetal cerebral embolisation to treat vein of Galen malformations at risk of urgent neonatal decompensation: study protocol for a clinical trial of safety and feasibility. BMJ Open. 2022 May 24;12(5):e058147. doi: 10.1136/bmjopen-2021-058147.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 13, 2020
• First Submitted That Met QC Criteria: June 13, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Abnormalities; Nervous System Malformations; Vascular Malformations; Intracranial Arterial Diseases; Arteriovenous Malformations; Central Nervous System Vascular Malformations; Intracranial Arteriovenous Malformations; Congenital Abnormalities; Vein of Galen Malformations
• Other Study ID Numbers: IRB-P00034727; 2020P000216 (Other Identifier: Partners Healthcare IRB)

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: Yes