Effect of Xenon and Therapeutic Hypothermia, on the Brain and on Neurological Outcome Following Brain Ischemia in Cardiac Arrest Patients (Xe-hypotheca)
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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 |
- 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 ]
- 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 ]
| Estimated Enrollment: | 110 |
| Study Start Date: | May 2009 |
| Estimated Study Completion Date: | June 2014 |
| Estimated Primary Completion Date: | December 2013 (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 |
Inclusion Criteria:
- Ventricular fibrillation or non-perfusive ventricular tachycardia as initial cardiac rhythm
- The 1st attempt at resuscitation by emergency medical personnel must appear within 15 minutes after the collapse
- 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
- Patient should be still unconscious in the emergency room
- Age: 18 - 80 years
- Obtained consent within 4 hours after arrival to the hospital
Exclusion criteria
- Hypothermia (< 30°C core temperature)
- Unconsciousness before cardiac arrest (cerebral trauma, spontaneous cerebral hemorrhages, intoxications etc.)
- Response to verbal commands after the return of spontaneous circulation and before randomization
- Pregnancy
- Coagulopathy
- Terminal phase of a chronic disease
- Systolic arterial pressure < 80 mmHg or mean arterial pressure < 60 mmHg for over 30 min period after ROSC
- Evidence of hypoxemia (arterial oxygen saturation < 85%) for > 15 minutes after ROSC and before randomization.
- Factors making participation in follow-up unlikely
- Enrolment in another study
Contacts and Locations| Contact: Timo T Laitio, MD, PhD | +358504653201 | timo.laitio@tyks.fi |
| United States, California | |
| Department of Anesthesia and Perioperative Care | Active, not recruiting |
| San Fransisco, California, United States | |
| Finland | |
| Department of Neurology, Meilahti, Helsinki University Hospital | Active, not recruiting |
| Helsinki, Finland, 340 | |
| Intensive Care Unit, Meilahti, Helsinki University Hospital | Recruiting |
| Helsinki, Finland, 340 | |
| Contact: Marja Hynninen, PhD marja.hynninen@hus.fi | |
| Principal Investigator: Marja Hynninen, PhD MD | |
| Sub-Investigator: Johanna Wennervirta, PhD, MD | |
| Sub-Investigator: Minna Bäcklund, PhD;MD | |
| Sub-Investigator: Päivi Silvasti, MD | |
| Sub-Investigator: Eija Nukarinen, MD | |
| Department of Radiology, HUSRontgen, Meilahti, Helsinki University Hospital | Active, not recruiting |
| Helsinki, Finland, 340 | |
| Department of Cardiology, Meilahti, Helsinki University Hospital | Active, not recruiting |
| Helsinki, Finland, 800 | |
| PET Centre | Active, not recruiting |
| Turku, Finland, 20521 | |
| Department of Radiology, Turku University Hospital | Active, not recruiting |
| Turku, Finland, 20521 | |
| Department of Neurology; Turku University Hospital | Active, not recruiting |
| Turku, Finland, 20521 | |
| Department of Internal Medicine, Division of Cardiology, Turku University Hospital | Active, not recruiting |
| Turku, Finland, 20521 | |
| Adult Intensive Care Unit, Turku University Hospital | Recruiting |
| Turku, Finland, 20521 | |
| Contact: Ruut Laitio, MD, PhD, EDIC ruut.laitio@tyks.fi | |
| Contact: Klaus Olkkola, Professor klaus.olkkola@tyks.fi | |
| Sub-Investigator: Olli Arola, MD | |
| Sub-Investigator: Ruut Laitio, MD, PhD | |
| Sub-Investigator: Emmi Ylikoski, MD, PhD | |
| Sub-Investigator: Juha Grönlund, MD, PhD | |
| Principal Investigator: | Timo T Laitio, MD, PhD | Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine |
More Information
Publications:
| 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 4, 2013 |
| Health Authority: | Finland: Finnish Medicines Agency |
Keywords provided by Turku University Hospital:
|
xenon hypothermia out-of-hospital cardiac arrest |
Additional relevant MeSH terms:
|
Brain Ischemia Heart Arrest Hypothermia Ischemia Brain Injuries Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Heart Diseases Body Temperature Changes Signs and Symptoms |
Pathologic Processes Craniocerebral Trauma Trauma, Nervous System Wounds and Injuries Xenon Anesthetics, Inhalation Anesthetics, General Anesthetics Central Nervous System Depressants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 22, 2013