Effect of Xenon and Therapeutic Hypothermia, on the Brain and on Neurological Outcome Following Brain Ischemia in Cardiac Arrest Patients (Xe-hypotheca)

This study has been completed.
Sponsor:
Collaborators:
Academy of Finland (Risto O Roine)
University of Turku
Information provided by (Responsible Party):
Timo Laitio, Turku University Hospital
ClinicalTrials.gov Identifier:
NCT00879892
First received: April 10, 2009
Last updated: January 16, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention Phase
Ischemic Brain Injury
Drug: xenon
Other: Hypothermia
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Turku University Hospital:

Primary Outcome Measures:
  • Primary outcome 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, reflected by various MRI techniques [ Time Frame: within 24 hours after treatment and 10 +/-2 days after cardiac arrest ] [ Designated as safety issue: Yes ]
    Power analysis was done with fractional anisotropy of diffusion tensor MRI


Secondary Outcome Measures:
  • Neurological outcome [ Time Frame: 6 months after cardiac arrest ] [ Designated as safety issue: Yes ]
  • A transthoracic echocardiography will be performed for all feasible patients to investigate cardiac safety of the treatments [ Time Frame: Before, during and after treatments ] [ Designated as safety issue: Yes ]
  • Mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Complication rate [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    epileptic status, severe bleeding, pneumonia, sepsis, pancreatitis, acute kidney injury according to RIFLE, pulmonary oedema, arrhythmias

  • Morbidity [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    cardiac and cerebral morbidity


Enrollment: 110
Study Start Date: May 2009
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Hypothermia and xenon Drug: xenon
Gas, 24 hour inhalation, en tidal target concentration 40%
Other: Hypothermia
24 hour, target core temperature 33
Active Comparator: Hypothermia Other: Hypothermia
24 hour, target core temperature 33

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ventricular fibrillation or non-perfusive ventricular tachycardia as initial cardiac rhythm
  2. The 1st attempt at resuscitation by emergency medical personnel must appear within 15 minutes after the collapse
  3. The cause for collapse should be considered primary as cardiogenic and the return of spontaneous circulation (ROSC) should have been gained in 45 minutes after the collapse
  4. Patient should be still unconscious in the emergency room
  5. Age: 18 - 80 years
  6. Obtained consent within 4 hours after arrival to the hospital

Exclusion criteria

  1. Hypothermia (< 30°C core temperature)
  2. Unconsciousness before cardiac arrest (cerebral trauma, spontaneous cerebral hemorrhages, intoxications etc.)
  3. Response to verbal commands after the return of spontaneous circulation and before randomization
  4. Pregnancy
  5. Coagulopathy
  6. Terminal phase of a chronic disease
  7. Systolic arterial pressure < 80 mmHg or mean arterial pressure < 60 mmHg for over 30 min period after ROSC
  8. Evidence of hypoxemia (arterial oxygen saturation < 85%) for > 15 minutes after ROSC and before randomization.
  9. Factors making participation in follow-up unlikely
  10. Enrolment in another study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879892

Locations
United States, California
Department of Anesthesia and Perioperative Care
San Fransisco, California, United States
Finland
Department of Radiology, HUSRontgen, Meilahti, Helsinki University Hospital
Helsinki, Finland, 340
Department of Neurology, Meilahti, Helsinki University Hospital
Helsinki, Finland, 340
Intensive Care Unit, Meilahti, Helsinki University Hospital
Helsinki, Finland, 340
Department of Cardiology, Meilahti, Helsinki University Hospital
Helsinki, Finland, 800
PET Centre
Turku, Finland, 20521
Adult Intensive Care Unit, Turku University Hospital
Turku, Finland, 20521
Department of Internal Medicine, Division of Cardiology, Turku University Hospital
Turku, Finland, 20521
Department of Neurology; Turku University Hospital
Turku, Finland, 20521
Department of Radiology, Turku University Hospital
Turku, Finland, 20521
Sponsors and Collaborators
Turku University Hospital
Academy of Finland (Risto O Roine)
University of Turku
Investigators
Principal Investigator: Timo T Laitio, MD, PhD Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Timo Laitio, Principal investigator, study group leader, Turku University Hospital
ClinicalTrials.gov Identifier: NCT00879892     History of Changes
Other Study ID Numbers: Eudra CT2009-009505-25
Study First Received: April 10, 2009
Last Updated: January 16, 2015
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by Turku University Hospital:
xenon
hypothermia
out-of-hospital cardiac arrest

Additional relevant MeSH terms:
Brain Injuries
Brain Ischemia
Brain Diseases
Heart Arrest
Hypothermia
Body Temperature Changes
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Craniocerebral Trauma
Heart Diseases
Nervous System Diseases
Signs and Symptoms
Trauma, Nervous System
Vascular Diseases
Wounds and Injuries
Xenon
Anesthetics
Anesthetics, General
Anesthetics, Inhalation
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2015