Effect of Xenon and Therapeutic Hypothermia, on the Brain and on Neurological Outcome Following Brain Ischemia in Cardiac Arrest Patients
Condition: Ischemic Brain Injury
MeSH terms: Brain Injuries; Brain Ischemia; Heart Arrest; Ischemia; Hypothermia
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): xenon; Hypothermia
Intervention type(s): Drug; Other
Intervention description(s): Gas, 24 hour inhalation, en tidal target concentration 40%; 24 hour, target core temperature 33
Intervention MeSH terms: Xenon
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: xenon; hypothermia; out-of-hospital cardiac arrest