Fetal Tracheal Balloon Study in Diaphragmatic Hernia

Phase 2 Fetal Tracheal Balloon (IDE G080077) Study in Diaphragmatic Hernia

The purpose of this phase 2 limited study is to examine whether prenatal intervention correct the lung underdevelopment associated with severe diaphragmatic hernia.

Study Overview

• Status: Terminated
• Conditions: Lung Disease; Diaphragmatic Hernia
• Intervention / Treatment: Device: Fetal tracheal obstruction with detachable balloon (device)

Detailed Description

Congenital diaphragmatic hernia (CDH) has traditionally been associated with very high mortality rates. Most infants died of pulmonary hypoplasia and severe pulmonary hypertension. This led to correction of CDH and pulmonary hypoplasia before birth. Unfortunately, maternal morbidity of open fetal surgery was significant and fetal mortality was very high (>60%). Moreover, the results of postnatal therapy for CDH improved dramatically, from less than 20% survival several decades ago to more than 70% today.

Fetal intervention has evolved as well, to a minimally invasive approach that involves a single endoscopic port and occlusion of the fetal trachea. While this has considerably decreased the morbidity and fetal mortality of the in utero procedure, its results do not exceed the overall (i.e., non-stratified) results of contemporary postnatal treatment. Most recently, a multicentric cooperative study under (Eurofoetus) has conducted a clinical trial comparing postnatal treatment with endoscopic fetal tracheal occlusion for the most severe forms of CDH. Results of the Eurofoetus trial and of a recent retrospective review involving European and North-American centers have shown the following: 1) It is possible to identify a specific subgroup of fetuses with CDH in whom survival can be predicted to be less than 10%, despite all current methods of postnatal treatment, 2) Survival of fetuses with predicted postnatal survival of 8% was >50% following endoscopic fetal tracheal occlusion, and 3) Fetal tracheal occlusion in that group resulted in an increase in lung size (LHR), from an average of 0.7 pre-intervention, to 1.7 post-intervention.

Based on the available research literature, the results of the Eurofoetus trial, and this institution's experience with endoscopic fetal surgery, we hypothesize that in the highest risk group of fetuses with congenital diaphragmatic hernia, where chances of survival is estimated at less than 10%, endoscopic fetal tracheal occlusion in late second trimester, with reversal of occlusion in mid-third trimester, allows catch-up lung growth and maturation and converts the condition into one with intermediate to good prognosis (predicted survival 50-60%). We propose to offer this form of treatment, under an FDA-approved Investigational Device Exemption (G080077), to eligible patients, on a case-by-case basis, after discussion before a multidisciplinary board.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital/Women & Infants' Hospital of Rhode Island

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Singleton pregnancies
• Isolated congenital diaphragmatic hernia
• Normal karyotype (amniocentesis)
• Initial diagnosis before 26 weeks gestation
• Competent cervix
• Severity of CDH: lung-to-head ratio (LHR) ≤0.8 at 22-26 weeks gestation
• Liver herniation in the chest
• Informed consent

Exclusion Criteria:

• Preterm labor, premature rupture of membranes or amniotic leak
• Significant maternal morbidity
• Minor (<18 years)

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: Detachable balloon; Intervention: Fetuses treated with endoscopic tracheal occlusion

Device: Fetal tracheal obstruction with detachable balloon (device); Fetal tracheal obstruction with detachable balloon (device): Endoscopic placement of a detachable balloon in the fetal trachea at 28-30 weeks gestation. - Ultrasound-guided puncture of balloon or, if not feasible, repeat endoscopic tracheoscopy with puncture and retrieval of the balloon at 34 weeks gestation.; Other Names: Goldvalve Balloon, nFocus Neuromedical, Inc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Newborn Survival at Birth	Newborn period (1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Newborn Survival at 30 Days		30 days
Maternal Complications		Intervention to 30 days postpartum
Fetal Morbidity	Fetal morbidity, fetal mortality	Intervention to delivery
Number of Participants With In Utero Lung Growth (LHR) >1.4	Inclusion criterion for the study is LHR<0.9 (extreme pulmonary hypoplasia). Given that LHR is relatively constant during 2nd and 3rd trimester of gestation, "In utero lung growth" is defined as LHR>1.4 (definition of mild/moderate pulmonary hypoplasia) within 2 weeks of intervention. Outcome measure = number of participants with LHR>1.4 at 2 weeks post-intervention	Intervention to 2 weeks post-intervention

Collaborators and Investigators

• Sponsor: Rhode Island Hospital
• Investigators: Principal Investigator: Francois I Luks, MD, PhD, Rhode Island Hospital

Publications and helpful links

General Publications

• Jani JC, Nicolaides KH, Gratacos E, Valencia CM, Done E, Martinez JM, Gucciardo L, Cruz R, Deprest JA. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009 Sep;34(3):304-10. doi: 10.1002/uog.6450.
• De Paepe ME, Johnson BD, Papadakis K, Sueishi K, Luks FI. Temporal pattern of accelerated lung growth after tracheal occlusion in the fetal rabbit. Am J Pathol. 1998 Jan;152(1):179-90.
• Wild YK, Piasecki GJ, De Paepe ME, Luks FI. Short-term tracheal occlusion in fetal lambs with diaphragmatic hernia improves lung function, even in the absence of lung growth. J Pediatr Surg. 2000 May;35(5):775-9. doi: 10.1053/jpsu.2000.6067.
• Luks FI, Wild YK, Piasecki GJ, De Paepe ME. Short-term tracheal occlusion corrects pulmonary vascular anomalies in the fetal lamb with diaphragmatic hernia. Surgery. 2000 Aug;128(2):266-72. doi: 10.1067/msy.2000.107373.
• Deprest JA, Flemmer AW, Gratacos E, Nicolaides K. Antenatal prediction of lung volume and in-utero treatment by fetal endoscopic tracheal occlusion in severe isolated congenital diaphragmatic hernia. Semin Fetal Neonatal Med. 2009 Feb;14(1):8-13. doi: 10.1016/j.siny.2008.08.010. Epub 2008 Oct 8.
• Bealer JF, Skarsgard ED, Hedrick MH, Meuli M, VanderWall KJ, Flake AW, Adzick NS, Harrison MR. The 'PLUG' odyssey: adventures in experimental fetal tracheal occlusion. J Pediatr Surg. 1995 Feb;30(2):361-4; discussion 364-5. doi: 10.1016/0022-3468(95)90590-1.
• Luks FI, Roggin KK, Wild YK, Piasecki GJ, Rubin LP, Lesieur-Brooks AM, De Paepe ME. Effect of lung fluid composition on type II cellular activity after tracheal occlusion in the fetal lamb. J Pediatr Surg. 2001 Jan;36(1):196-201. doi: 10.1053/jpsu.2001.20051.
• De Paepe ME, Johnson BD, Papadakis K, Luks FI. Lung growth response after tracheal occlusion in fetal rabbits is gestational age-dependent. Am J Respir Cell Mol Biol. 1999 Jul;21(1):65-76. doi: 10.1165/ajrcmb.21.1.3511.
• De Paepe ME, Papadakis K, Johnson BD, Luks FI. Fate of the type II pneumocyte following tracheal occlusion in utero: a time-course study in fetal sheep. Virchows Arch. 1998 Jan;432(1):7-16. doi: 10.1007/s004280050128.
• Papadakis K, Luks FI, De Paepe ME, Piasecki GJ, Wesselhoeft CW Jr. Fetal lung growth after tracheal ligation is not solely a pressure phenomenon. J Pediatr Surg. 1997 Feb;32(2):347-51. doi: 10.1016/s0022-3468(97)90208-6.
• Luks FI, Deprest JA, Gilchrist BF, Peers KH, van der Wildt B, Steegers EA, Vandenberghe K. Access techniques in endoscopic fetal surgery. Eur J Pediatr Surg. 1997 Jun;7(3):131-4. doi: 10.1055/s-2008-1071072.
• Yang SH, Nobuhara KK, Keller RL, Ball RH, Goldstein RB, Feldstein VA, Callen PW, Filly RA, Farmer DL, Harrison MR, Lee H. Reliability of the lung-to-head ratio as a predictor of outcome in fetuses with isolated left congenital diaphragmatic hernia at gestation outside 24-26 weeks. Am J Obstet Gynecol. 2007 Jul;197(1):30.e1-7. doi: 10.1016/j.ajog.2007.01.016.
• Luks FI, Carr SR, Muratore CS, O'Brien BM, Tracy TF. The pediatric surgeons' contribution to in utero treatment of twin-to-twin transfusion syndrome. Ann Surg. 2009 Sep;250(3):456-62. doi: 10.1097/SLA.0b013e3181b45794.

Helpful Links

• Information about congenital diaphragmatic hernia - The Fetal Treatment Program

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: August 26, 2009
• First Submitted That Met QC Criteria: August 26, 2009
• First Posted (Estimate): August 27, 2009

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: ECMO; Diaphragm; Trachea; Neonatal death; Lung development; Lung growth; Tracheal occlusion
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Lung Diseases; Hernia; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic
• Other Study ID Numbers: G080077