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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 10
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- 未提供
研究组 & 干预措施
Hypothermia and xenon
干预措施: xenon (Drug)
Hypothermia and xenon
干预措施: Hypothermia (Other)
Hypothermia
干预措施: Hypothermia (Other)
结局指标
主要结局
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
时间窗: within 24 hours after treatment and 10 +/-2 days after cardiac arrest
Power analysis was done with fractional anisotropy of diffusion tensor MRI
次要结局
- Neurological outcome(6 months after cardiac arrest)
- Complication rate(7 days)
- Morbidity(6 months)
- Mortality(6 months)
- A transthoracic echocardiography will be performed for all feasible patients to investigate cardiac safety of the treatments(Before, during and after treatments)
研究者
Timo Laitio
Principal investigator, study group leader
Turku University Hospital