Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02230072 |
| Other study ID # |
H-34680 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
July 2014 |
| Est. completion date |
November 2024 |
Study information
| Verified date |
March 2024 |
| Source |
Baylor College of Medicine |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of the study is to evaluate the maternal and fetal outcomes of a new technique
for the fetoscopic repair of fetal MMC at Texas Children's Hospital Pavilion for Women.
The investigators hypothesis is that this minimally invasive technique is feasible, and that
this approach will have the same efficacy as open fetal surgery for MMC, but with
significantly less maternal-fetal risk. Both mother and baby will benefit from the surgery.
The fetus will have a repaired MMC defect, and the mother will not have a uterine incision
(hysterotomy). A hysterotomy increases the risk of uterine rupture and requires that all
subsequent deliveries are by cesarean section. There may also be a decreased risk of Pre-term
Premature Rupture Of Membranes (PPROM) and prematurity when compared with the current open
operation. Finally, a vaginal delivery is possible following the fetoscopic fetal surgery if
the baby is shown to have a skin covered repair.
Description:
Spina bifida can be a devastating neurological congenital anomaly . It results from
incomplete closure of the neural tube between 22 and 28 embryological days. Its incidence is
approximately 1-2 per 1,000 births. It is considered the most common congenital anomaly of
the central nervous system that is compatible with life.
1. The most frequent form is myelomeningocele (MMC), characterized by the extrusion of the
spinal cord into a sac filled with cerebrospinal fluid (CSF), and is associated with
lower limb paralysis and bowel and bladder dysfunction.
2. The majority of MMCs can be diagnosed between 14 and 20 weeks of gestation. MMC is
associated with Chiari II malformation, which includes a constellation of anomalies such
as hindbrain herniation, brainstem abnormalities, low-lying venous sinuses and a small
posterior fossa.The Chiari II malformation can have deleterious effects on motor,
cranial nerve and cognitive functions. Postnatally most MMC patients develop
hydrocephalus and require a ventriculoperitoneal shunt. Shunts require lifelong
monitoring and have a high failure rate due to infection, obstruction, and fracture.
Experimental studies using animal models have shown that prenatal coverage of a spina
bifida-like lesion can preserve neurological function and reduce or reverse hindbrain
herniation.These studies suggest a "two-hit" hypothesis in which the ultimate neurologic
deficit results from a combination of the failure of normal neural-tube closure (first hit)
with secondary spinal cord injury resulting from prolonged exposure of sensitive neural
elements to the amniotic fluid (second hit mechanism).
Based on this hypothesis, open fetal surgical repair of MMC was proposed, and the recent
publication of the NICHD sponsored randomized controlled trial demonstrated clear neonatal
benefit of open in-utero fetal surgical repair of MMC. The study showed a reduction in the
incidence of hydrocephalus and in the radiographic severity of hindbrain herniation (relative
risk: 0.67; 95% confidence interval: 0.56-0.81).
Open in-utero fetal surgery is not without risk and the NICHD study (MOMS Trial) showed an
elevation in maternal-fetal morbidity/risk when compared to the postnatally treated group,
including higher risk for chorioamniotic separation (26% vs. 0%, respectively), maternal
pulmonary edema (6% vs. 0%), oligohydramnios (21% vs. 0%), placental abruption (6% vs. 0%),
spontaneous membrane rupture (46%; RR: 6.15; 95% CI: 2.75-13.78), spontaneous labor (38%; RR:
2.80, 95%CI: 1.51-5.18), maternal blood transfusion (9%; RR: 7.18; 95%CI: 0.90-57.01), and
preterm delivery before 34 weeks (46%; RR: 9.2; 95%CI: 3.81-22.19). The reason for the
increased incidence of these complications is related to the nature of the open fetal
procedure, which involves a multi-faceted invasive approach including maternal laparotomy,
large hysterotomy with uterine edge stapling, and open fetal repair of the spina bifida
defect that may involve manipulation and exposure of the fetus for a significant amount of
time.
Fetal endoscopic surgery has progressed rapidly over the past decades and the investigators
are now able to perform a number of intricate procedures inside the uterus with specially
designed instruments. These procedures include laser therapy for Twin-twin-transfusion
syndrome, fetal cystoscopy and fulguration of posterior urethral valves, release of amniotic
bands, and placement of various shunts and balloons inside fetal structures and cavities
(peritoneal, pleural, cardiac, and trachea).
Fetoscopy offers a less invasive therapeutic option that could reduce a number of the
morbidities (both maternal and fetal) related to open fetal procedures.
A few animal studies and some clinical human experience with fetoscopic repair of MMC have
been reported showing the feasibility of covering the defect with a patch and sealant, or
even in performing a full repair. These repairs have been accomplished using at least two
(and sometimes more) entry ports through the uterine wall. Kohl et al. in Germany, have
demonstrated the feasibility of performing a complete percutaneous fetoscopic repair of MMC
using carbon dioxide to distend the uterus and provide a dry working area for the surgeon to
perform the repair.
These investigators described a two-layer covering technique using an absorbable patch
(Durasis, Cook, Germany) and sutures. However, while they showed that the procedure is
feasible, their percutaneous technique with complete two layer surgical closure of the defect
using sutures was associated with prolonged operative time and significant maternal and
obstetrical morbidities.
Fetoscopy in a CO2 gas filled uterus has been recently reported by groups in Bonn, Germany
(Kohl et al) and Sao Paulo, Brazil (Pedreira et al). The fetoscopic technique the
investigators use has been developed and tested in a fetal sheep model of MMC by the
investigators group and others (Peiro et al).
This fetoscopy technique has evolved over time to a 2-port technique developed by our team in
Houston, Texas and its feasibility and applicability to the human uterus and fetus have been
demonstrated and published (Belfort et al, 2017) and demonstrate an improved degree of
flexibility in terms of access to the fetus regardless of placental location. The technique
is designed to decrease the maternal risks of open uterus fetal surgery while maintaining a
similar level of fetal benefit as seen in the MOMS trial.
The investigators technique employs an open abdomen/exteriorized (but closed) uterus
methodology that allows the minimally invasive multi-layer closure of the fetal neural tube
using the same closed skin repair currently employed at Baylor College of Medicine/Texas
Children's Fetal Center using the open uterus approach. The technique employs a novel
approach to low pressure uterine distention using the same carbon dioxide gas 8-12 mmHg that
others attempting fetoscopic repair have used, but employing a much lower gas flow rate and
pressure. In addition, our technique (as compared with the percutaneous method) allows
improved access to the fetus in anterior placentation, ability to manipulate and maintain the
fetus in the required position, and optimal port placement resulting from the exteriorized
maternal uterus.
In addition, because of the exteriorized uterus and the optimal placement this allows, we
require only two access ports and these can be sutured into the uterus allowing a closed seal
and minimizing gas leakage. The use of humidified, warmed CO2, which we pioneered in fetal
surgery, decreases membrane disruption and may prolong gestation without rupture of the
membranes. Finally, recent advances in miniature surgical instruments (Storz 1.5 - 3mm
surgical sets) allow unprecedented flexibility which enables a full surgical repair to be
performed via a fetoscopic approach.
In preparation for the human trial we were able to perform, in a sheep model, dual access
port fetoscopic neural tube closure using a 12 F cannula, a second 9F cannula, a cover patch,
and a medical sealant with similar results to that seen with open fetal surgical repair in
the same sheep model.26
We have now completed almost 50 cases using our 2 port exteriorized technique with results
that are reflect our initial hypothesis (Belfort et al , 2017). As with any technique there
have been advances in instrumentation and technique and the study is ongoing investigating
the multilayer closure technique.
In this protocol, the repair of the open neural tube defect will follow the same principles
as we use in open repairs currently being done at this institution. This involves release of
the placode, dissection of the surrounding skin and attempted primary closure of the defect
using a Durepair patch, a muscle or duro-fascial flap, and available skin. In those cases
where we are able to complete the procedure with full skin closure of the defect, the only
difference between the open uterus procedure and the fetoscopic procedure, will be that the
surgery will be done fetoscopically rather than through an open uterine incision. If we are
unable to close the skin primarily despite best fetoscopic efforts, the option of
performing/completing the repair as an open procedure exists and will be offered to the
patient. The patient is monitored in hospital until ready for discharge.
Approximately 6 weeks after the surgery a post-procedure fetal MRI will be performed. If
there is evidence of good closure of the neural tube defect and reversal of the Chiari II
malformation, a vaginal delivery can be attempted based on obstetric criteria. Patients will
be followed in person every 3-4 months after birth to 12 months at the Spina Bifida Clinic at
TCH. Remaining visits will be yearly up to 5 years. If this is not possible, questionnaire(s)
will be mailed to the child's parents and records will be requested from the treating
neurosurgeon on this same schedule.
