Congenital Heart DiseaseNEUROHEARTNCT02996630
Assessing Neurodevelopment in Congenital Heart Disease.
A study testing Sonography, Magnetic Resonance Imaging and Bailey Test in people with Congenital Heart Disease, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.
Trial summary
Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns per year. Children with CHD are a known risk population for brain injury, with neurodevelopmental alterations shown over time in up to 50% of cases. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Congenital Heart Disease
- What is being tested?
- Sonography, Magnetic Resonance Imaging and Bailey Test
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteSpain
- Study dates
- May 2013to May 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Single pregnancies
- Major Congenital Heart Disease
- Informed Consent Signed
Who cannot join
- Major extra-cardiac malformations
- Parental Refusal to participate
- Maternal Chronic Disease
- Multiple Pregnancies
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitari Vall d'Hebrón
Barcelona, Barcelona, 08035
Irene Ribera, Dr, 934893000 ext. 3086, irene.ribera@vhir.org
Elisa Llurba, Dr, 934893000 ext. 3086, irene.ribera@vhir.org
About this study
Official title: Abnormal Neurodevelopment Detection in Congenital Heart Disease: Predictive Methods Based on Prenatal and Postnatal Factors.
Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns per year. Children with CHD are a known risk population for brain injury, with neurodevelopmental alterations shown over time in up to 50% of cases. No adequate description exists of the type of neurocognitive anomalies or risk factors associated with CHD, and consequently no prognostic markers that may allow identification of high-risk cases are available.
Read the detailed description
The main objectives of this study are: 1. to describe the neurodevelopmental outcome of patients with CHD at 24 months of age; 2. identify the subgroup with poorer outcome; and 3. evaluate the utility of fetal and postnatal diagnostic techniques for early detection of patients at risk for altered neurological outcomes.
Seven Spanish referral centers for CHD included in the research network on maternal and child health currently participating in this prospective multicentric case-control coordinated study. Fetuses with CHD (transposition of great arteries, tetralogy of Fallot, hypoplastic left heart syndrome and septal defects) will be studied from 24 weeks of gestation to 2 years of age. Diagnostic tests will be repeated throughout the study in all patients, from the fetal period to 24 months of age, and will include: fetal cerebral hemodynamic Doppler assessment, functional echocardiography, brain MRI, regional cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers analysis. Neurodevelopmental assessment will be made at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. From this data, statistical analysis will select the most useful as predictors of damage; to be then combined and create algorithms for predicting brain damage and poor neurodevelopment. Once description has been made, we will proceed to identify amongst our results, children with the poorest neurological outcome and remark possible common prenatal and early life markers in them as well as the CHD severity they present.
While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. Evidence available does not allow clinicians to assess on neurological prognosis although has opened up the possibility of finding prenatal markers of brain damage. Even though, no prospective studies have been performed until now. We present a multicentric prospective study able to recruit enough fetal CHD affected pregnancies to obtain neurological prognostic tools.
- Conditions
- Congenital Heart Disease
- Being tested
- Sonography, Magnetic Resonance Imaging, Bailey Test, Surgical intervention, Brain monitoring
- Keywords
- LVOTO, Fallot, Great Arteries Transposition
- Medical subject headings
- Heart Defects, Congenital, Transposition of Great Vessels
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SonographyProcedure or surgery
Fetal Ultrasound exploration
Magnetic Resonance ImagingDevice
Fetal MRI for brain study
Bailey TestOther
Neurodevelopment paediatric assessment test performed at 2 years of age.
Surgical interventionProcedure or surgery
Congenital Heart Disease repair
Brain monitoringProcedure or surgery
EEG and continuous brain oximetry before surgery.
cord blood sampleProcedure or surgery
Cord blood samples will be taken after birth in both groups.
| Study group | Role | What they receive |
|---|---|---|
| Healthy fetuses | Other | Pregnant patients carrying a healthy fetus. Interventions in this group will be: cord blood sample, sonography, Magnetic Resonance Imaging and bailey test. Receives: Procedure: Sonography; Device: Magnetic Resonance Imaging; Other: Bailey Test; Procedure: cord blood sample |
| Congenital Hearth Disease | Other | Pregnant patients carrying a fetus with a moderate-severe congenital heart disease Interventions in this group will be: cord blood sample, sonography, Magnetic Resonance Imaging, Surgical intervention, brain monitoring and bailey test. Receives: Procedure: Sonography; Device: Magnetic Resonance Imaging; Other: Bailey Test; Procedure: Surgical intervention; Procedure: Brain monitoring; Procedure: cord blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bailey-III test punctuation
Results in pediatric Bailey-III test scale
Measured: 45 minutes
Secondary outcomes (11)
Biparietal diameter (mm)
Biparietal diameter (mm) measured with MRI
Measured: one day
Lateral sulcus depth
Lateral sulcus depth (mm) measured with MRI
Measured: one day
Cerebral insula
Insula (mm) measured with MRI
Measured: one day
Brain biometries
Calcarine sulcus depth (mm)
Measured: one day
Cerebral cingulata sulcus
Cingulata sulcus depth (mm) measured with MRI
Measured: one day
Corpus callosum
Corpus callosum (mm) measured with MRI
Measured: one day
Cerebellum
Cerebellum vermis (mm) measured with MRI
Measured: one day
Umbilical doppler
Umbilical artery pulsatility index
Measured: one day
Middle cerebral artery doppler
Middle cerebral artery pulsatility index
Measured: one day
Angiogenic PLGF (placental growth factor)
Placental growth factor in maternal serum
Measured: Two days
Angiogenic s-FLt (soluble fms-like tyrosine kinase)
Soluble fms-like tyrosine kinase factor in maternal serum
Measured: Two days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2016 (estimated)
- Study startMay 2013
- Primary completionMay 2017 (estimated)
- Study completionMay 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Hospital Universitari Vall d'Hebron Research InstituteThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Sant Joan de Deu, Hospital Universitario La Paz, Hospital Universitario 12 de Octubre, Hospital General Universitario Gregorio Marañon, Fundacion Dexeus
- Responsible party
- Sponsor
- Investigators
- Elisa Llurba, MD, PhD, Study director, Hospital Universitari Vall d'Hebrón
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02996630
- Sponsor's protocol ID
- PR(AMI)317/2012
- Acronym
- NEUROHEART
- Status last verified
- Oct 2016
- First submitted
- 31 Oct 2016
- Last updated
- 19 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900. doi: 10.1016/s0735-1097(02)01886-7.
PubMed 12084585Bellinger DC, Jonas RA, Rappaport LA, Wypij D, Wernovsky G, Kuban KC, Barnes PD, Holmes GL, Hickey PR, Strand RD, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med. 1995 Mar 2;332(9):549-55. doi: 10.1056/NEJM199503023320901.
PubMed 7838188Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B, Rohlicek C, Tchervenkov C. Neurodevelopmental status of newborns and infants with congenital heart defects before and after open heart surgery. J Pediatr. 2000 Nov;137(5):638-45. doi: 10.1067/mpd.2000.109152.
PubMed 11060529Masoller N, Martinez JM, Gomez O, Bennasar M, Crispi F, Sanz-Cortes M, Egana-Ugrinovic G, Bartrons J, Puerto B, Gratacos E. Evidence of second-trimester changes in head biometry and brain perfusion in fetuses with congenital heart disease. Ultrasound Obstet Gynecol. 2014 Aug;44(2):182-7. doi: 10.1002/uog.13373. Epub 2014 Jul 8.
PubMed 24687311Ruiz A, Cruz-Lemini M, Masoller N, Sanz-Cortes M, Ferrer Q, Ribera I, Martinez JM, Crispi F, Arevalo S, Gomez O, Perez-Hoyos S, Carreras E, Gratacos E, Llurba E. Longitudinal changes in fetal biometry and cerebroplacental hemodynamics in fetuses with congenital heart disease. Ultrasound Obstet Gynecol. 2017 Mar;49(3):379-386. doi: 10.1002/uog.15970.
PubMed 27214694Ribera I, Ruiz A, Sanchez O, Eixarch E, Antolin E, Gomez-Montes E, Perez-Cruz M, Cruz-Lemini M, Sanz-Cortes M, Arevalo S, Ferrer Q, Vazquez E, Vega L, Dolader P, Montoliu A, Boix H, Simoes RV, Masoller N, Sanchez-de-Toledo J, Comas M, Bartha JM, Galindo A, Martinez JM, Gomez-Roig L, Crispi F, Gomez O, Carreras E, Cabero L, Gratacos E, Llurba E. Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol. BMC Pediatr. 2019 Sep 10;19(1):326. doi: 10.1186/s12887-019-1689-y.
PubMed 31506079
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Abnormal Neurodevelopment Detection in Congenital Heart Disease: Predictive Methods Based on Prenatal and Postnatal Factors.
- ClinicalTrials.gov ID
- NCT02996630
- Acronym / sponsor ID
- NEUROHEART / PR(AMI)317/2012
- Conditions
- Congenital Heart Disease
- Keywords
- LVOTO, Fallot, Great Arteries Transposition
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research InstituteUniversity, hospital or other
- Collaborators
- Hospital Sant Joan de Deu, Hospital Universitario La Paz, Hospital Universitario 12 de Octubre, Hospital General Universitario Gregorio Marañon, Fundacion Dexeus
- Study start
- May 2013
- Primary completion
- May 2017 (estimated)
- Study completion
- May 2018 (estimated)
- First posted
- 19 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns per year. Children with CHD are a known risk population for brain injury, with neurodevelopmental alterations shown over time in up to 50% of cases. No adequate description exists of the type of neurocognitive anomalies or risk factors associated with CHD, and consequently no prognostic markers that may allow identification of high-risk cases are available.
Detailed description
The main objectives of this study are: 1. to describe the neurodevelopmental outcome of patients with CHD at 24 months of age; 2. identify the subgroup with poorer outcome; and 3. evaluate the utility of fetal and postnatal diagnostic techniques for early detection of patients at risk for altered neurological outcomes.
Seven Spanish referral centers for CHD included in the research network on maternal and child health currently participating in this prospective multicentric case-control coordinated study. Fetuses with CHD (transposition of great arteries, tetralogy of Fallot, hypoplastic left heart syndrome and septal defects) will be studied from 24 weeks of gestation to 2 years of age. Diagnostic tests will be repeated throughout the study in all patients, from the fetal period to 24 months of age, and will include: fetal cerebral hemodynamic Doppler assessment, functional echocardiography, brain MRI, regional cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers analysis. Neurodevelopmental assessment will be made at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. From this data, statistical analysis will select the most useful as predictors of damage; to be then combined and create algorithms for predicting brain damage and poor neurodevelopment. Once description has been made, we will proceed to identify amongst our results, children with the poorest neurological outcome and remark possible common prenatal and early life markers in them as well as the CHD severity they present.
While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. Evidence available does not allow clinicians to assess on neurological prognosis although has opened up the possibility of finding prenatal markers of brain damage. Even though, no prospective studies have been performed until now. We present a multicentric prospective study able to recruit enough fetal CHD affected pregnancies to obtain neurological prognostic tools.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy fetuses | Other | Procedure: Sonography, Device: Magnetic Resonance Imaging, Other: Bailey Test, Procedure: cord blood samplePregnant patients carrying a healthy fetus. Interventions in this group will be: cord blood sample, sonography, Magnetic Resonance Imaging and bailey test. |
| Congenital Hearth Disease | Other | Procedure: Sonography, Device: Magnetic Resonance Imaging, Other: Bailey Test, Procedure: Surgical intervention, Procedure: Brain monitoring, Procedure: cord blood samplePregnant patients carrying a fetus with a moderate-severe congenital heart disease Interventions in this group will be: cord blood sample, sonography, Magnetic Resonance Imaging, Surgical intervention, brain monitoring and bailey test. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Single pregnancies
- Major Congenital Heart Disease
- Informed Consent Signed
Key exclusion criteria (4 listed)
- Major extra-cardiac malformations
- Parental Refusal to participate
- Maternal Chronic Disease
- Multiple Pregnancies
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 |
|---|---|---|
| SonographyFetal Ultrasound exploration | Procedure or surgery | Congenital Hearth Disease, Healthy fetuses |
| Magnetic Resonance ImagingFetal MRI for brain study | Device | Congenital Hearth Disease, Healthy fetuses |
| Bailey TestNeurodevelopment paediatric assessment test performed at 2 years of age. | Other | Congenital Hearth Disease, Healthy fetuses |
| Surgical interventionCongenital Heart Disease repair | Procedure or surgery | Congenital Hearth Disease |
| Brain monitoringEEG and continuous brain oximetry before surgery. | Procedure or surgery | Congenital Hearth Disease |
| cord blood sampleCord blood samples will be taken after birth in both groups. | Procedure or surgery | Congenital Hearth Disease, Healthy fetuses |
Primary outcome
Bailey-III test punctuation
Time frame: 45 minutes
Results in pediatric Bailey-III test scale
11 secondary outcomes
Biparietal diameter (mm)
Time frame: one day
Lateral sulcus depth
Time frame: one day
Cerebral insula
Time frame: one day
Brain biometries
Time frame: one day
Cerebral cingulata sulcus
Time frame: one day
Corpus callosum
Time frame: one day
Cerebellum
Time frame: one day
Umbilical doppler
Time frame: one day
Middle cerebral artery doppler
Time frame: one day
Angiogenic PLGF (placental growth factor)
Time frame: Two days
Angiogenic s-FLt (soluble fms-like tyrosine kinase)
Time frame: Two days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2016.
- Results publication: PubMed 12084585Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900. doi: 10.1016/s0735-1097(02)01886-7.
- Results publication: PubMed 7838188Bellinger DC, Jonas RA, Rappaport LA, Wypij D, Wernovsky G, Kuban KC, Barnes PD, Holmes GL, Hickey PR, Strand RD, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med. 1995 Mar 2;332(9):549-55. doi: 10.1056/NEJM199503023320901.
- Results publication: PubMed 11060529Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B, Rohlicek C, Tchervenkov C. Neurodevelopmental status of newborns and infants with congenital heart defects before and after open heart surgery. J Pediatr. 2000 Nov;137(5):638-45. doi: 10.1067/mpd.2000.109152.
- Results publication: PubMed 24687311Masoller N, Martinez JM, Gomez O, Bennasar M, Crispi F, Sanz-Cortes M, Egana-Ugrinovic G, Bartrons J, Puerto B, Gratacos E. Evidence of second-trimester changes in head biometry and brain perfusion in fetuses with congenital heart disease. Ultrasound Obstet Gynecol. 2014 Aug;44(2):182-7. doi: 10.1002/uog.13373. Epub 2014 Jul 8.
- Results publication: PubMed 27214694Ruiz A, Cruz-Lemini M, Masoller N, Sanz-Cortes M, Ferrer Q, Ribera I, Martinez JM, Crispi F, Arevalo S, Gomez O, Perez-Hoyos S, Carreras E, Gratacos E, Llurba E. Longitudinal changes in fetal biometry and cerebroplacental hemodynamics in fetuses with congenital heart disease. Ultrasound Obstet Gynecol. 2017 Mar;49(3):379-386. doi: 10.1002/uog.15970.
- Derived from this study: PubMed 31506079Ribera I, Ruiz A, Sanchez O, Eixarch E, Antolin E, Gomez-Montes E, Perez-Cruz M, Cruz-Lemini M, Sanz-Cortes M, Arevalo S, Ferrer Q, Vazquez E, Vega L, Dolader P, Montoliu A, Boix H, Simoes RV, Masoller N, Sanchez-de-Toledo J, Comas M, Bartha JM, Galindo A, Martinez JM, Gomez-Roig L, Crispi F, Gomez O, Carreras E, Cabero L, Gratacos E, Llurba E. Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol. BMC Pediatr. 2019 Sep 10;19(1):326. doi: 10.1186/s12887-019-1689-y.
- Individual participant dataSharing planned: No
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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.
Elisa Llurba, MD, PhD study director
Hospital Universitari Vall d'Hebrón
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sonography, Magnetic Resonance Imaging and Bailey Test in people with Congenital Heart Disease, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.
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 3 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 19 Dec 2016. 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 Spain. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Irene Ribera, MD (934893000 ext. 3086, irene.ribera@vhir.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bailey-III test punctuation (time frame: 45 minutes). 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 NCT02996630, which also lists 6 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 19 Dec 2016.