Diaphragmatic HerniaPhase 2NCT00966823
Fetal Tracheal Balloon Study in Diaphragmatic Hernia
A Phase 2 study testing Fetal tracheal obstruction with detachable balloon (device) in people with Diaphragmatic Hernia and Lung Disease, run by Rhode Island Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Diaphragmatic Hernia, Lung Disease
- What is being tested?
- Fetal tracheal obstruction with detachable balloon (device)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Jan 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Preterm labor, premature rupture of membranes or amniotic leak
- Significant maternal morbidity
- Minor (<18 years)
Trial locations and contacts
1 site in 1 country.
United States1 site
Rhode Island Hospital/Women & Infants' Hospital of Rhode Island
Providence, Rhode Island, 02903
About this study
Official title: 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.
Read the 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.
- Conditions
- Diaphragmatic Hernia, Lung Disease
- Being tested
- Fetal tracheal obstruction with detachable balloon (device)
- Keywords
- Diaphragm, Trachea, Lung development, Lung growth, Tracheal occlusion, ECMO, Neonatal death
- Medical subject headings
- Hernia, Diaphragmatic, Lung Diseases, Tracheal Diseases, Perinatal Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fetal tracheal obstruction with detachable balloon (device)Device
Also called Goldvalve Balloon, nFocus Neuromedical, Inc.
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.
| Study group | Role | What they receive |
|---|---|---|
| Detachable balloon | Experimental | Intervention: Fetuses treated with endoscopic tracheal occlusion Receives: Device: Fetal tracheal obstruction with detachable balloon (device) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Newborn Survival at Birth
Measured: Newborn period (1 day)
Secondary outcomes (4)
Newborn Survival at 30 Days
Measured: 30 days
Maternal Complications
Measured: Intervention to 30 days postpartum
Fetal Morbidity
Fetal morbidity, fetal mortality
Measured: 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
Measured: Intervention to 2 weeks post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2009 (estimated)
- Study startSep 2008
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: Device no longer available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Diaphragmatic HerniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rhode Island Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francois Luks, Rhode Island Hospital
- Investigators
- Francois I Luks, MD, PhD, Principal investigator, Rhode Island Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00966823
- Sponsor's protocol ID
- G080077
- Status last verified
- May 2017
- First submitted
- 26 Aug 2009
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 7738765Luks 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.
PubMed 11150464Luks 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.
PubMed 10923003Wild 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.
PubMed 10813348De 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.
PubMed 10385594De 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.
PubMed 9463582De 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.
PubMed 9422535Papadakis 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.
PubMed 9044151Luks 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.
PubMed 9241495Jani 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.
PubMed 19658113Deprest 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.
PubMed 18845492Yang 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.
PubMed 17618746Luks 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.
PubMed 19644353
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Fetal Tracheal Balloon (IDE G080077) Study in Diaphragmatic Hernia
- ClinicalTrials.gov ID
- NCT00966823
- Acronym / sponsor ID
- G080077
- Conditions
- Diaphragmatic Hernia, Lung Disease
- Keywords
- Diaphragm, Trachea, Lung development, Lung growth, Tracheal occlusion, ECMO, Neonatal death
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Device no longer available
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Rhode Island HospitalUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 27 Aug 2009 (estimated)
- Results
- Posted 30 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this phase 2 limited study is to examine whether prenatal intervention correct the lung underdevelopment associated with severe diaphragmatic hernia.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Detachable balloon | Experimental | Device: Fetal tracheal obstruction with detachable balloon (device)Intervention: Fetuses treated with endoscopic tracheal occlusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Singleton pregnancies
- Isolated congenital diaphragmatic hernia
- Normal karyotype (amniocentesis)
- Initial diagnosis before 26 weeks gestation
- Competent cervix
Key exclusion criteria (3 listed)
- Preterm labor, premature rupture of membranes or amniotic leak
- Significant maternal morbidity
- Minor (<18 years)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fetal tracheal obstruction with detachable balloon (device)Also: Goldvalve Balloon, nFocus Neuromedical, Inc.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. | Device | Detachable balloon |
Primary outcome
Newborn Survival at Birth
Time frame: Newborn period (1 day)
4 secondary outcomes
Newborn Survival at 30 Days
Time frame: 30 days
Maternal Complications
Time frame: Intervention to 30 days postpartum
Fetal Morbidity
Time frame: Intervention to delivery
Number of Participants With In Utero Lung Growth (LHR) >1.4
Time frame: Intervention to 2 weeks post-intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7738765Bealer 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.
- Background: PubMed 11150464Luks 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.
- Background: PubMed 10923003Luks 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.
- Background: PubMed 10813348Wild 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.
- Background: PubMed 10385594De 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.
- Background: PubMed 9463582De 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.
- Background: PubMed 9422535De 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.
- Background: PubMed 9044151Papadakis 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.
- Background: PubMed 9241495Luks 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.
- Background: PubMed 19658113Jani 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.
- Background: PubMed 18845492Deprest 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.
- Background: PubMed 17618746Yang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francois I Luks, MD, PhD principal investigator
Rhode Island Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fetal tracheal obstruction with detachable balloon (device) in people with Diaphragmatic Hernia and Lung Disease, run by Rhode Island Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Newborn Survival at Birth (time frame: Newborn period (1 day)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00966823, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2017.