Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02769026 |
| Other study ID # |
1R01NS096714-01A1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2017 |
| Est. completion date |
March 1, 2021 |
Study information
| Verified date |
April 2021 |
| Source |
University of Pittsburgh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This multicenter study will validate a panel of serum, imaging, and clinical biomarkers to
classify patient outcome early after out-of-hospital pediatric cardiac arrest. Results are
expected to have a positive and immediate impact in advancing clinical care and outcomes for
these children. This work will provide clinicians, families, and researchers with superior
tools to assess the severity of brain injury early after resuscitation in order to know who
is at risk of brain injury and may benefit from neuroprotective interventions, to monitor
response to these interventions, to plan rehabilitation strategy, and to optimize the design
of research studies that test novel interventions to improve neurological outcome after
cardiac arrest.
Description:
Children with cardiac arrest (CA) have mortality rates of 50-90%, largely due to neurological
failure as part of the post-resuscitation syndrome. There is a critical gap of knowledge and
tools to accurately classify outcome after pediatric CA. Physical examination and laboratory
testing inadequately assess the severity of neurologic injury and outcome. Hazards of
misclassification include risking adverse effects from ineffective therapies and
non-treatment of ostensibly well patients who later are found to have neurologic deficits.
Early and accurate identification of the eventual severity of neurologic injury would allow
for timely neuroprotective interventions and/or more targeted testing of new therapies in
specific risk populations. The long term objective is to improve the neurological outcome of
children surviving CA. In this study, investigators will model and validate serum and imaging
biomarkers of brain injury with empirical support, and assess their accuracy together with
clinical variables in classifying outcome after pediatric CA. The central hypothesis is that
serum and imaging biomarkers of brain injury, together with clinical variables, will
critically aid in the early classification of favorable outcome after pediatric CA (Vineland
Adaptive Behavior Scales score [VABS] > 70) 1 year after pediatric CA in a multicenter
prospective study (8-12 centers and 248 subjects). Strong preliminary data supports this
hypothesis, and biomarkers will be tested for outcome classification accuracy in the
following 3 specific aims:
Aim 1) Serum biomarkers of neuronal (neuron specific enolase and ubiquitin carboxy-terminal
hydrolase-L1) and glial injury (S100b and glial fibrillary acidic protein) Aim 2) Regional
(occipital-parietal cortex, basal ganglia, and thalamus) brain MRI (T1/T2 and
diffusion-weighted imaging) and magnetic resonance spectroscopy (MRS) biomarkers of neuronal
injury (N-acetyl-aspartate) and energy failure (lactate) Aim 3 will model the combination of
strong serum and imaging biomarkers of brain injury with clinical variables. We will assess
serum biomarkers of brain mitochondrial injury with potential for novel therapeutic targets
(cardiolipin and oxidized cardiolipin) in an exploratory aim. This proposed research is
innovative, because a combined panel of serum and imaging biomarkers with clinical variables
to accurately classify outcome after pediatric CA will be prospectively developed and
optimized. These proposed aims leverage recent pilot successes and should generate accurate
and reliable models of biomarkers that markedly improve post-resuscitation clinical care in
children after CA. Furthermore, these results are expected to have a positive impact in
advancing neurocritical care for these children, with forthcoming development of a serum
biomarker point of care test and biomarker panels that will accurately classify risk of
unfavorable outcome for clinicians and researchers needing to stratify by severity of injury,
to monitor response to therapy, and ultimately to assist in their rehabilitation and
recovery.
