Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME)

Australian and New Zealand Intensive Care Research Centre

Status

Unknown

Conditions

Out-Of-Hospital Cardiac Arrest

Treatments

Other: Targeted normocapnia (Standard care)

Other: Targeted therapeutic mild hypercapnia

Study type

Interventional

Funder types

Other

Identifiers

NCT03114033

ANZIC-RC/SB001

Details and patient eligibility

About

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.

Full 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.

Enrollment

1,700 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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