NCT03114033

Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest

TAME Cardiac Arrest Trial: Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest: A Phase III Multi-Centre Randomised Controlled Trial

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 1,700 (actual)
• Sponsor: Australian and New Zealand Intensive Care Research Centre · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Out-Of-Hospital Cardiac Arrest

Interventions

Type	Name	Description
OTHER	Targeted therapeutic mild hypercapnia	Patients allocated to the TTMH protocol will be sedated to achieve moderate to deep sedation (a target Richmond Agitation Scale Score of -4). Arterial blood gases and end- tidal carbon dioxide levels will be measured at baseline and then used to guide respiratory rate adjustments of minute ventilation to remain within the target PaCO2 range of 50-55 mmHg. Arterial blood gases will be repeated every 4 hours for 24 hours following randomisation or if end-tidal carbon dioxide values change \>5 mmHg
OTHER	Targeted normocapnia (Standard care)	Patients allocated to the standard care (TN) protocol will be managed according to current practice and in accordance with ILCOR guidelines which recommend maintaining normocapnia in these patients. They will be sedated to achieve moderate to deep sedation (a target Richmond Agitation Scale Score of - 4). Arterial blood gases and end-tidal carbon dioxide levels will be measured at baseline and then used to guide respiratory rate adjustments of minute ventilation to remain within the target PaCO2 range of 35-45 mmHg. Arterial blood gases will be repeated every 4 hours for 24 hours following randomisation or if end-tidal carbon dioxide values change \>5 mmHg.

Timeline

• Start date: 2018-02-15
• Primary completion: 2022-12-01
• Completion: 2022-12-01
• First posted: 2017-04-14
• Last updated: 2022-04-20

Locations

52 sites across 14 countries: Australia, Belgium, Denmark, Finland, France, Ireland, Italy, Netherlands, New Zealand, Norway, Saudi Arabia, Slovenia, Sweden, United Kingdom