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Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME)

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ClinicalTrials.gov Identifier: NCT03114033
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : February 16, 2018
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
Health Research Board, Ireland
Information provided by (Responsible Party):
Australian and New Zealand Intensive Care Research Centre

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.

Condition or disease Intervention/treatment Phase
Out-Of-Hospital Cardiac Arrest Other: Targeted therapeutic mild hypercapnia Other: Targeted normocapnia (Standard care) Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1700 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: A Randomised, Parallel Groups, Assessor Blinded, Clinical Trial
Primary Purpose: Treatment
Official Title: TAME Cardiac Arrest Trial: Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest: A Phase III Multi-Centre Randomised Controlled Trial
Actual Study Start Date : February 15, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cardiac Arrest

Arm Intervention/treatment
Experimental: Targeted therapeutic mild hypercapnia
Target arterial carbon dioxide range of 50-55 mmHg for 24 hours following randomisation
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

Active Comparator: Targeted normocapnia (Standard care)
Target arterial carbon dioxide range of 35-45 mmHg for 24 hours following randomisation
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.




Primary Outcome Measures :
  1. Neurological outcome [ Time Frame: 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 :
  1. Mortality at intensive care unit discharge [ Time Frame: 6 months after randomisation ]
    Mortality at intensive care unit discharge

  2. Mortality at hospital discharge [ Time Frame: 6 months after randomisation ]
    Mortality at hospital discharge

  3. Health-related Quality of Life (EQ-5D-5L) [ Time Frame: 6 months after randomisation ]
    Health-related Quality of Life (EQ-5D-5L)

  4. modified Rankin scale (mSR) [ Time Frame: 6 months after randomisation ]
    modified Rankin scale (mSR)

  5. Cerebral Performance Category (CPC) [ Time Frame: 6 months after randomisation ]
    Cerebral Performance Category (CPC)

  6. Montreal Cognitive Assessment (MoCA-blind) [ Time Frame: 6 months after randomisation ]
    Montreal Cognitive Assessment (MoCA-blind)


Other Outcome Measures:
  1. Quality Adjust Life Years (QALYs) [ Time Frame: 6 months after randomisation ]
    Quality Adjust Life Years (QALYs)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03114033


Contacts
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Contact: Glenn M Eastwood, RN, PhD +61399030035 ext 30035 glenn.eastwood@austin.org.au
Contact: Rinaldo Bellomo, MD, PhD +61394965992 ext 5992 rinaldo.bellomo@austin.org.au

Locations
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Australia, Victoria
Austin Health Recruiting
Melbourne, Victoria, Australia, 3084
Contact: Glenn M Eastwood, RN, PhD    +61394964835    glenn.eastwood@austin.org.au   
Contact: Rinaldo Bellomo, MD    +61394965992    rinaldo.bellomo@austin.org.au   
Sponsors and Collaborators
Australian and New Zealand Intensive Care Research Centre
National Health and Medical Research Council, Australia
Health Research Board, Ireland
Investigators
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Principal Investigator: Glenn M Eastwood, RN, PhD Monash University

Publications of Results:
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Responsible Party: Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier: NCT03114033     History of Changes
Other Study ID Numbers: ANZIC-RC/SB001
First Posted: April 14, 2017    Key Record Dates
Last Update Posted: February 16, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Australian and New Zealand Intensive Care Research Centre:
Cardiac Arrest
Intensive Care Unit
Therapeutic Mild Hypercapnia
Normocapnia
Mortality
Neurological function

Additional relevant MeSH terms:
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Heart Arrest
Out-of-Hospital Cardiac Arrest
Hypercapnia
Heart Diseases
Cardiovascular Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms