Clinical Trial: Fetoscopic Endoluminal Tracheal Occlusion (FETO) for Severe Left Diaphragmatic Hernia (CDH)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Pilot Trial of Fetoscopic Endoluminal Tracheal Occlusion (FETO) in Fetuses With Severe Left Congenital Diaphragmatic Hernia (CDH)

Brief Summary:

Despite advances in prenatal diagnosis and postnatal therapies, including extracorporeal membrane oxygenation (ECMO), inhaled nitric oxide therapy, and ventilator strategies that minimize ventilator-induced lung injury, morbidity and mortality rates for babies with congenital diaphragmatic hernia (CDH) remain high. The survival relates to the degree of prenatal lung compression and the subsequent impairment of pulmonary function following delivery. Prenatal assessment by ultrasound or magnetic resonance imaging allows to estimate the severity by relating the circumference of the lung contralateral to the hernia to the fetal head circumference lung to head ratio (LHR) and by noting the degree of upward herniation of the liver. Based on the observed to expected lung to head ratio (O/E LHR), prenatally diagnosed congenital diaphragmatic hernia can be prognostically assessed. While overall survival of congenital diaphragmatic hernia is approximately 60%, an O/E LHR <25% is associated with survival between 11-24%.

The rationale for fetal therapy in severe congenital diaphragmatic hernia is to restore adequate lung growth for neonatal survival. Prenatal tracheal occlusion obstructs the normal egress of lung fluid during pulmonary development leading to increased lung tissue stretch, increased cell proliferation, and accelerated lung growth. European colleagues have developed intrauterine endoscopic techniques (fetoscopy) to position and remove endoluminal tracheal balloons in utero (fetoscopic endotracheal occlusion = FETO). Recently, the Belgium group published summary results of FETO showing an improved survival in 175 patients with isolated left CDH from 24% to 49%. Our goal with this pilot study is to study the feasibility of implementing FETO therapy in the most severe group of fetuses with left CDH (O/E LHR < 30%). which will be considered in two subgroups. Those wi

Detailed Summary:

Study Procedures The FETO feasibility study is an un-blinded non-randomized single arm pilot study being conducted at the Johns Hopkins Hospital.

Pregnant women will be screened for protocol inclusion and exclusion criteria and recruited.

Comprehensive fetal evaluations will be completed at the Johns Hopkins Center for Fetal Therapy to confirm eligibility. This includes an ultrasound, magnetic resonance imaging, a fetal echocardiogram and fetal genetic studies to identify cases with isolated CDH. Once eligibility is confirmed, participation for FETO treatment will be offered. The voluntary nature of participation will be stressed throughout. Willingness and logistics of the participant to remain under supervision of the Center for Fetal Therapy at the Johns Hopkins Hospital, while the fetal airway is occluded will also be discussed in detail. Informed written consent will be obtained prior to any study related procedures.

Study design Participants will undergo FETO with standardized preoperative, intraoperative, post-operative care, and delivery. The FETO will be timed between 27+0 to 29+6 weeks gestation for fetuses with an O/E LHR <25% and between 30+0 to 31+6 weeks gestation for fetuses with an O/E LHR between 25% to <30%. The procedure will be performed under local anesthesia with IV sedation or regional spinal/epidural (as done currently for shunts and laser procedures). Prophylactic tocolysis using indomethacin will begin preoperatively. Fetal analgesia and immobilization will consist of fentanyl, atropine and vecuronium. A 10 Fr cannula, 1.3 mm fetoscope within a 3.3 mm sheath (Karl Storz, Tuttlingen, Germany), and a detachable balloon occlusion (BALTACCI-BDPE, Balt, Montmorency, France) system will be used. Participants will receive IV magnesium sulfate for br
Sponsor: Johns Hopkins University

Current Primary Outcome: Successful balloon insertion and removal [ Time Frame: 4 to 7 weeks ]

The feasibility of performing the procedure, managing the pregnancy during the period of tracheal occlusion, and removal of the device prior to delivery at Johns Hopkins Hospital.


Original Primary Outcome: Successful balloon insertion and removal [ Time Frame: 7 weeks ]

The feasibility of performing the procedure, managing the pregnancy during the period of tracheal occlusion, and removal of the device prior to delivery at Johns Hopkins Hospital.


Current Secondary Outcome:

  • Survival [ Time Frame: 28 days after delivery ]
    The neonatal survival of participants receiving FETO expressed as a percentage of the total number of participants undergoing the procedure.
  • Percentage of lung growth [ Time Frame: 4 to 7 weeks ]
    The percentage of size increase in the contralateral fetal lung as related to the pre-procedure lung size


Original Secondary Outcome:

  • Survival [ Time Frame: 28 days after delivery ]
    The neonatal survival of participants receiving FETO expressed as a percentage of the total number of participants undergoing the procedure.
  • Percentage of lung growth [ Time Frame: 7 weeks ]
    The percentage of size increase in the contralateral fetal lung as related to the pre-procedure lung size


Information By: Johns Hopkins University

Dates:
Date Received: August 17, 2015
Date Started: August 2015
Date Completion: July 2019
Last Updated: May 3, 2017
Last Verified: May 2017