Ischemic Brain Injury Clinical Trial
Official title:
Phase 2 Study of Effect of Xenon, in Combination With Therapeutic Hypothermia, on the Brain and on Neurological Outcome Following Brain Ischemia in Cardiac Arrest Patients
The main purpose of this study is to explore whether xenon is neuroprotective in humans. In addition, the purpose is to explore the underlying mechanisms for the possible synergistic neuroprotective interaction of xenon and hypothermia in patients suffering cerebral ischemia post cardiac arrest, by undertaking brain imaging to evaluate their effects on cerebral hypoxia, neuronal loss and mitochondrial dysfunction. In addition, the investigators aim to correlate these findings with neurological outcome to determine surrogate markers of favourable clinical outcome at six months.
If cardiac resuscitation is successful, the state-of-the-art management is to actively cool
these patients into a state of moderate hypothermia (32-34º C) for 24 hours in an intensive
care unit. Guidelines regarding the use of hypothermia following witnessed cardiac arrest
have been formally adopted by the European Resuscitation Council as well as the American
Heart Association. Therapeutic hypothermia provides a significant but moderate improvement
in these patients. Thus, strategies designed to increase the efficacy of therapeutic
hypothermia are needed.
Preclinical animal studies have now demonstrated a remarkable neuroprotective interaction
with hypothermia in a synergistic manner. The data suggest that xenon's neuroprotective
effect can be triggered with subanesthetic concentrations in humans when combined with
modest hypothermia.
The aim of this study is to explore whether xenon is neuroprotective in humans. We also
explore whether xenon in combination with standard hypothermia treatment has better
neuroprotective effect than can be achieved with the hypothermia treatment alone in the
patients who have experienced global ischemic brain injury after out-of-hospital cardiac
arrest (OHCA).
Hundred-and- ten patients who have experienced ventricular fibrillation or non-perfusive
ventricular tachycardia as initial cardiac rhythm will be enrolled and they will be
randomized into two treatment groups: 1) standard hypothermia treatment for 24 hours, 2)
xenon inhalation combined with standard hypothermia treatment for 24 hours.
Sophisticated brain imaging techniques will be performed before intervention (i.e. standard
CT scan), within 24 hours after intervention (i.e. positron emission tomography), and on day
3 and on day 10 after cardiac arrest (i.e. various proton magnetic resonance imaging
techniques) to identify ischemic burden, injured tissue and deranged energy metabolism in
the brain.
Our objective is to show a significant reduction in the degree of severity of the ischemic
brain injury in the hypothermia+Xenon group as compared with the hypothermia group.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT00983723 -
Clinical Proteomic Research for the Brain
|
N/A |