Non-invasive removal of the Smart tracheal occlusion device for fetal congenital diaphragmatic hernia: a single-arm, open-label, phase 1 study.

Abstract

One of the drawbacks of fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) is the need for a second intervention to establish airway patency. In this first-in-human study, we aimed to evaluate a novel tracheal occlusion device (Smart-TO) that spontaneously deflates when in close proximity to a strong magnetic field. We conducted two parallel single-centre, single-arm, open-label trials in Paris, France, and Leuven, Belgium. Eligibility criteria included patient age 18 years or more, singleton pregnancy with CDH, and severe or moderate pulmonary hypoplasia in left-sided CDH; in Leuven, eligibility criteria also included severe hypoplasia in right-sided and bilateral CDH. Fetal lung size was assessed by measuring the observed-to-expected lung-to-head ratio by ultrasonography. Data for baseline demographics were self-reported and collected at the screening visit. Insertion of the Smart-TO balloon was scheduled between 27⁺⁰ weeks and 31⁺⁶ weeks of gestation. Balloon deflation was scheduled between 34⁺⁰ weeks and 34⁺⁶ weeks (or earlier, if clinically indicated) by exposure to the magnetic field of a MRI machine, and ultrasonography was then done to confirm balloon deflation. The primary endpoint was balloon deflation, with expulsion of the balloon from the fetal airways at birth as a coprimary outcome in the Paris arm of the study. The primary outcome was reported with its 95% CI using the continuity-corrected score method for all patients with the investigational medical device in place at the time of deflation. Safety analysis was conducted for all patients in whom FETO was attempted. These trials are registered with ClinicalTrials.gov (NCT04931212 [Paris]) and NCT05100693 [Leuven]) and have been completed. Between Aug 4, 2021 and Jan 15, 2024, 48 patients were enrolled. Of these, 47 patients underwent FETO, and the Smart-TO was successfully placed in 46 fetuses. Median gestational age at FETO was 29⁺² weeks (28⁺⁵-30⁺¹ weeks). After placement, there was one spontaneous balloon deflation and one unexplained intrauterine fetal death. In all other patients, MRI machine-induced balloon deflation was attempted. The deflation rate was 100% (95% CI 92-100). At birth, the empty balloon was outside the airways in all infants. There were two cases of tracheomalacia in survivors, both with symptom resolution by the time of discharge from neonatal intensive care. There were 14 neonatal deaths, all attributed to pulmonary hypoplasia. Five adverse events were considered likely related to the device (of a total of 84), and no serious adverse events (of a total of 40) were related to the Smart-TO device. This study shows effective magnetic resonance-induced deflation of the Smart-TO balloon and supports short-term safety. These findings constitute an important advance in fetal surgery for CDH, eliminating the need for a second intrauterine procedure. Clinical Council for Research and Education (Klinische Onderzoeks-en Opleidingsraad) of the University Hospitals of Leuven and Assistance Publique-Hôpitaux de Paris. Investigational devices (Smart-TO) were provided free of charge to patients and institutions by BS-MTI.