Early FETO for Severe Congenital Diaphragmatic Hernia

"Early" Versus "Standard" Fetal Endoscopic Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia - a Randomized Controlled Trial

Congenital diaphragmatic hernia (CDH) is associated high mortality and morbidity, mainly in those cases with severe forms where there are extremely reduced lung volumes, liver herniation and decreased abnormal pulmonary vascularization. Fetal endoscopic tracheal occlusion performed between 26 and 30 weeks (standard FETO) has been shown to increase fetal pulmonary size and vascularity, and to improve infant survival in isolated severe CDH. Fetal pulmonary response followed FETO can be used to predict outcome and is dependent on the size of the fetal lung prior to the procedure.

We hypothesize that performing an earlier FETO, between 22-24 weeks, fetuses with severe form of CDH will have a better fetal pulmonary response and higher chance of surviving.

Study Overview

• Status: Unknown
• Conditions: Congenital Diaphragmatic Hernia
• Intervention / Treatment: Other: Fetal endoscopic tracheal occlusion

Detailed Description

We pretend to investigate if "early FETO" will improve the survival rate and the fetal pulmonary response, by conducting a randomized controlled trial comparing the results with those fetuses that undergo to "standard FETO" (between 26-28 weeks).

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rodrigo Ruano, MD PhD; Phone Number: (5511)95739188; Email: rodrigoruano@usp.br
• Study Contact Backup: Name: Eugenia MA Salustiano, RN; Phone Number: (5511)2661-6209; Email: eugeniaassuncao@hotmail.com

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-010
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Fetuses with isolated congenital diaphragmatic hernia (normal fetal karyotype and absence of any associated structural anomaly);
• Gestational age established by last menstruation and/or first trimester ultrasonography;
• Prenatal diagnosis of congenital diaphragmatic hernia before 24 weeks of gestation
• Severe congenital diaphragmatic hernia (at 24 weeks, lung-to-head ratio <1.0 and at least 1/3 of the liver herniated into the fetal thorax)
• written informed consent (by the patient)

Exclusion Criteria:

• Preterm premature rupture of the membranes before randomization
• Preterm labor before randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard FETO; Group of fetus that undergo fetal endoscopic tracheal occlusion between 26 0/7 weeks and 28 6/7 weeks.	Other: Fetal endoscopic tracheal occlusion; FETO will be performed by placing a detachable balloon inside fetal trachea; Other Names: FETO or fetal endoscopic traqueal occlusion
Experimental: Early FETO; Group of fetus that undergo fetal endoscopic tracheal occlusion between 22 0/7 weeks and 24 6/7 weeks.	Other: Fetal endoscopic tracheal occlusion; FETO will be performed by placing a detachable balloon inside fetal trachea; Other Names: FETO or fetal endoscopic traqueal occlusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant survival rate	Percentage of survivors at 6 months of life	6 months of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postnatal severe pulmonary arterial hypertension (PAH)	Severe PAH will be considered when the neonate presents with profound cyanosis associated with echocardiographic continuous right-to-left shunting through a persistent 'ductus arteriosus' and a persistent difference in pre- to postductal saturation gradient >20%, despite the use of intake Nitric Oxide (iNO).	30 days of life
Respiratory morbidity	Need for ventilatory support and/or oxygen dependency.	6 months of life

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
obstetrical complications (morbidity)	Preterm premature rupture of the membranes (<37 weeks); Extremely preterm premature rupture of the membranes (<32 weeks); Preterm delivery (birth <37 weeks of gestation); Extremely preterm delivery (birth <32 weeks); Placental abruption; Chorioamnionitis and maternal infection	pregnancy

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: University of Sao Paulo
• Investigators: Principal Investigator: Rodrigo Ruano, MD PhD, Faculdade de Medicina da Universidade de Sao Paulo

Publications and helpful links

General Publications

• Ruano R, Duarte SA, Pimenta EJ, Takashi E, da Silva MM, Tannuri U, Zugaib M. Comparison between fetal endoscopic tracheal occlusion using a 1.0-mm fetoscope and prenatal expectant management in severe congenital diaphragmatic hernia. Fetal Diagn Ther. 2011;29(1):64-70. doi: 10.1159/000311944. Epub 2010 Apr 10.
• Ruano R, Yoshisaki CT, da Silva MM, Ceccon ME, Grasi MS, Tannuri U, Zugaib M. A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia. Ultrasound Obstet Gynecol. 2012 Jan;39(1):20-7. doi: 10.1002/uog.10142. Epub 2011 Dec 14.
• Ruano R, da Silva MM, Campos JA, Papanna R, Moise K Jr, Tannuri U, Zugaib M. Fetal pulmonary response after fetoscopic tracheal occlusion for severe isolated congenital diaphragmatic hernia. Obstet Gynecol. 2012 Jan;119(1):93-101. doi: 10.1097/AOG.0b013e31823d3aea.
• Harrison MR, Keller RL, Hawgood SB, Kitterman JA, Sandberg PL, Farmer DL, Lee H, Filly RA, Farrell JA, Albanese CT. A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med. 2003 Nov 13;349(20):1916-24. doi: 10.1056/NEJMoa035005.
• 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.
• Deprest J, Gratacos E, Nicolaides KH; FETO Task Group. Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results. Ultrasound Obstet Gynecol. 2004 Aug;24(2):121-6. doi: 10.1002/uog.1711. Erratum In: Ultrasound Obstet Gynecol. 2004 Oct;24(5):594.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: November 14, 2012
• First Submitted That Met QC Criteria: November 14, 2012
• First Posted (Estimate): November 21, 2012

Study Record Updates

• Last Update Posted (Estimate): December 17, 2013
• Last Update Submitted That Met QC Criteria: December 16, 2013
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: congenital diaphragmatic hernia; fetoscopy; fetal endoscopic tracheal occlusion; pulmonary hypoplasia; fetal surgery; fetal lung
• Additional Relevant MeSH Terms: Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Hernia; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic
• Other Study ID Numbers: 8353/12