Fetal Tracheal Balloon Study in Diaphragmatic Hernia

Lung Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00966823
• Other study ID #: G080077
• Status: Terminated
• Phase: Phase 2
• First received: August 26, 2009
• Last updated: May 23, 2017
• Start date: September 2008
• Est. completion date: January 2015

Study information

• Verified date: May 2017
• Source: Rhode Island Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Diaphragmatic Hernia
• Hernia
• Hernia, Diaphragmatic
• Hernias, Diaphragmatic, Congenital
• Lung Disease
• Lung Diseases

Intervention

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.

Locations

Country	Name	City	State
United States	Rhode Island Hospital/Women & Infants' Hospital of Rhode Island	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Rhode Island Hospital

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Jani JC, Nicolaides KH, Gratacós E, Valencia CM, Doné 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Newborn Survival at Birth		Newborn period (1 day)
Secondary	Newborn Survival at 30 Days		30 days
Secondary	Maternal Complications		Intervention to 30 days postpartum
Secondary	Fetal Morbidity	Fetal morbidity, fetal mortality	Intervention to delivery
Secondary	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

External Links

•   Information about congenital diaphragmatic hernia - The Fetal Treatment Program
•   The Fetal Treatment Program Home