TAME Cardiac Arrest Trial: Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest: A Phase III Multi-Centre Randomised Controlled Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 1,700
- 试验地点
- 103
- 主要终点
- Neurological outcome
研究概览
简要总结
The TAME Cardiac Arrest trial will study the ability of higher arterial carbon dioxide (PaCO2) levels to reduce brain damage, comparing giving patients 'normal' to 'slightly higher than normal' blood PaCO2 levels and assessing their ability to return to normal life-tasks. It will be the largest trial ever conducted in heart attack patients in the intensive care unit. This therapy is cost free and, if shown to be effective, will improve thousands of lives, transform clinical practice, and yield major savings.
详细描述
Cardiac arrest is a common and catastrophic event with substantial human and financial costs. It is well understood that cardiac arrest leads to brain injury. However, what is not widely appreciated is that, after circulation has been restored, cerebral hypoperfusion continues. Ongoing cerebral vasoconstriction and cerebral hypoxia has been demonstrated using technologies that include positron emission tomography, ultrasound, jugular bulb oxygen saturation and cerebral oximetry.
A likely mechanism responsible for sustained early cerebral hypoperfusion relates to impaired cerebrovascular auto-regulation. Such impaired cerebral auto-regulation may make even a normal arterial carbon dioxide tension (PaCO2) (the major physiological regulator of cerebral blood flow) insufficient to achieve and maintain adequate cerebral perfusion and, consequently, cerebral oxygenation. However, PaCO2 is the major determinant of cerebral blood flow and an increased PaCO2 (hypercapnia) markedly increases cerebral blood flow. Moreover, arterial carbon dioxide is modifiable and, as such, is a potential therapeutic target.
The TAME Cardiac Arrest Trial is a definitive phase III multi-centre randomised controlled trial in resuscitated cardiac arrest patients. This trial will determine whether targeted therapeutic mild hypercapnia (TTMH) applied during the first 24 hours of mechanical ventilation in the intensive care unit (ICU) improves neurological outcome at 6 months compared to standard care (targeted normocapnia (TN).
Supported by compelling preliminary data, significant improvements in patient outcomes are achievable with this proposed simple and cost free therapy. Recruiting 1,700 patients, for multiple sites in many countries, this will be the largest trial ever conducted involving resuscitated cardiac arrest patients admitted to the ICU. If the TAME Cardiac Arrest Trial confirms that TTMH is effective, its findings will improve the lives of many, transform clinical practice and yield major economic gains worldwide.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
A Randomised, Parallel Groups, Assessor Blinded, Clinical Trial
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult (age ≥18 years or older)
- •Out-of-hospital cardiac arrest of a presumed cardiac or unknown cause
- •Sustained ROSC - defined as 20 minutes with signs of circulation without the need for chest compressions
- •Unconscious (FOUR-score motor response of <4, not able to obey verbal commands after sustained ROSC) (Appendix D)
- •Eligible for intensive care without restrictions or limitations
- •Within <180 minutes of ROSC
排除标准
- •Unwitnessed cardiac arrest with an initial rhythm of asystole
- •Temperature on admission <30oC
- •On ECMO prior to ROSC
- •Obvious or suspected pregnancy
- •Intracranial bleeding
- •Severe chronic obstructive pulmonary disorder (COPD) with long-term home oxygen therapy
结局指标
主要结局
Neurological outcome
时间窗: 6 months following enrolment
Proportion of patients with a favourable (score ≥5) neurological outcome as assessed using the Glasgow Outcomes Score Extended (GOSE) method.
次要结局
- Mortality at 6 months(6 months after randomisation)
- Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest (IQCODE)(6 months after randomisation)
- Mortality at intensive care unit discharge(6 months after randomisation)
- Mortality at hospital discharge(6 months after randomisation)
- Health-related Quality of Life (EQ-5D-5L)(6 months after randomisation)
- modified Rankin scale (mRS)(6 months after randomisation)
- Montreal Cognitive Assessment (MoCA-blind)(6 months after randomisation)
- Symbol Digit Modality Test(6 months after randomisation)