Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest
- Conditions
- Out-Of-Hospital Cardiac Arrest
- Interventions
- Other: Targeted therapeutic mild hypercapniaOther: Targeted normocapnia (Standard care)
- Registration Number
- NCT03114033
- Brief 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1700
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Targeted therapeutic mild hypercapnia Targeted therapeutic mild hypercapnia Target arterial carbon dioxide range of 50-55 mmHg for 24 hours following randomisation Targeted normocapnia (Standard care) Targeted normocapnia (Standard care) Target arterial carbon dioxide range of 35-45 mmHg for 24 hours following randomisation
- Primary Outcome Measures
Name Time Method Neurological outcome 6 months following enrolment Proportion of patients with a favourable (score ≥5) neurological outcome as assessed using the Glasgow Outcomes Score Extended (GOSE) method.
- Secondary Outcome Measures
Name Time Method Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest (IQCODE) 6 months after randomisation IQCODE
Mortality at intensive care unit discharge 6 months after randomisation Mortality at intensive care unit discharge
Mortality at hospital discharge 6 months after randomisation Mortality at hospital discharge
Health-related Quality of Life (EQ-5D-5L) 6 months after randomisation Health-related Quality of Life (EQ-5D-5L) at 6 months
Mortality at 6 months 6 months after randomisation Mortality at 6 months
modified Rankin scale (mRS) 6 months after randomisation modified Rankin scale (mRS) with favourable score of equal to or less than 3
Montreal Cognitive Assessment (MoCA-blind) 6 months after randomisation Montreal Cognitive Assessment (MoCA-blind) at 6 months
Symbol Digit Modality Test 6 months after randomisation SDMT at 6 months
Trial Locations
- Locations (52)
University Hospital Galway
🇮🇪Galway, Ireland
University Hospital Ghent
🇧🇪Gent, Belgium
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
The Northern Hospital
🇦🇺Epping, Victoria, Australia
Footscray Hospital-Western Health
🇦🇺Melbourne, Victoria, Australia
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Ballarat Base Hospital
🇦🇺Ballarat, Victoria, Australia
Ziekenhuis Oost-Limburg AV
🇧🇪Genk, Belgium
St. James's Hospital
🇮🇪Dublin, Ireland
Alfred Health
🇦🇺Melbourne, Victoria, Australia
Sunshine Hospital-Western Health
🇦🇺Melbourne, Victoria, Australia
Flinders Medical Centre
🇦🇺Adelaide, South Australia, Australia
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Nepean Hospital
🇦🇺Penrith, New South Wales, Australia
Wollongong Hospital
🇦🇺Wollongong, New South Wales, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Nambour Hospital
🇦🇺Sunshine Coast, Queensland, Australia
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
Sunshine Coast University Hospital
🇦🇺Sunshine Coast, Queensland, Australia
University Hospital Geelong
🇦🇺Geelong, Victoria, Australia
Austin Health
🇦🇺Melbourne, Victoria, Australia
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Cliniques Universitaires de Bruxelles Hospital Erasme
🇧🇪Bruxelles, Belgium
CHRU Jean Minjoz Besancon
🇫🇷Besancon, Franche Comte, France
Beaumont Hospital
🇮🇪Dublin, Ireland
Ospedale San Raffaele
🇮🇹Milan, Italy
Amsterdam University Medical Centre
🇳🇱Amsterdam, Netherlands
Auckland City Hospital DCCM
🇳🇿Grafton, Auckland, New Zealand
Christchurch Hospital
🇳🇿Riccarton, Christchurch, New Zealand
Middlemore Hospital
🇳🇿Otahuhu, Auckland, New Zealand
Auckland City Hospital CVICU
🇳🇿Grafton, Auckland, New Zealand
North Shore Hospital
🇳🇿Auckland, New Zealand
Wellington Regional Hospital
🇳🇿Newtown, Wellington, New Zealand
Rotorua Hospital
🇳🇿Rotorua, New Zealand
Oslo University Hospital - Ullevål
🇳🇴Oslo, Norway
King Abdulaziz Medical City
🇸🇦Riyadh, Saudi Arabia
Skane Region-Helsingborg
🇸🇪Helsingborg, Sweden
Skane Region Malmö
🇸🇪Malmö, Sweden
University Medical Centre Maribor
🇸🇮Maribor, Slovenia
Queen Alexandra Hospital Portsmouth
🇬🇧Cosham, Portsmouth, United Kingdom
Royal Victoria Hospital Belfast
🇬🇧Belfast, United Kingdom
Birmingham University Hospital
🇬🇧Birmingham, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Bristol Royal Infirmary
🇬🇧Bristol, United Kingdom
University Hospital Wales
🇬🇧Cardiff, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Royal Berkshire Hospital
🇬🇧Reading, United Kingdom
Royal Darwin Hospital
🇦🇺Tiwi, Northern Territory, Australia