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Trial registered on ANZCTR


Registration number
ACTRN12617000036314
Ethics application status
Approved
Date submitted
16/12/2016
Date registered
10/01/2017
Date last updated
23/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase III multi-centre randomised controlled trial to evaluate the ability of slightly higher than normal carbon dioxide levels, compared to normal carbon dioxide levels, to reduce brain damage in resuscitated cardiac arrest patients admitted to the intensive care unit.
Scientific title
Targeted therapeutic mild hypercapnia after resuscitated cardiac arrest: A phase III multi-centre randomised controlled trial
Secondary ID [1] 290781 0
None
Universal Trial Number (UTN)
Trial acronym
The TAME Cardiac Arrest trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Out-of-hospital cardiac arrest 301394 0
Condition category
Condition code
Cardiovascular 301139 301139 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients allocated to the targeted therapeutic mild hypercapnia protocol will be sedated as per unit gudelines and at the clinical discretion of the treating intensive care doctors 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 for 24 hours following randomisation.. Arterial blood gases will be repeated every 4 hours for 24 hours following randomisation or if end-tidal carbon dioxide values change >5 mmHg. Adjustments to be made to the minute ventilation in order to stay within the target PaCO2 range will be made at the clinical discretion of the treating intensive care doctors. Strategies to monitor adherence to the target PaCO2 range will be via respiratory rate monitoring that displays a continuous record of PaCo2 values and as recorded on the participant's physiological observation chart while in the intensive care unit.
Intervention code [1] 296693 0
Treatment: Other
Comparator / control treatment
Patients allocated to the standard care (targeted normocapnia) 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 35-45 mmHg for 24 hours following randomisation.. Arterial blood gases will be repeated every 4 hours for 24 hours following randomisation or if end-tidal carbon dioxide values change >5 mmHg.
Control group
Active

Outcomes
Primary outcome [1] 300542 0
The proportion of patients with a favourable neurological outcome as assessed by the Glasgow Outcomes Scale Extended (GOSE) method. The GOSE uses an 8-level scale from death (1) to upper good recovery (8) and can be administered by proxy or direct patient interview.. A GOSE outcome is deemed to be favourable if a patient scores greater or equal to 5.
Timepoint [1] 300542 0
Assessed at 6 months following enrolment administered by proxy or direct patient interview.
Secondary outcome [1] 330273 0
Mortality status at intensive care unit (ICU) discharge
Timepoint [1] 330273 0
A review of hospital records will be performed to determine this outcome at the time of intensive care unit (ICU) discharge.
Secondary outcome [2] 330274 0
Mortality status at hospital discharge
Timepoint [2] 330274 0
A review of hospital records will be performed to determine this outcome at the time of hospital discharge.
Secondary outcome [3] 330275 0
Mortality status at 6 months
Timepoint [3] 330275 0
Assessed at 6 months from enrolment.assessed via hospital record review or direct contact with the participant or their next of kin
Secondary outcome [4] 330276 0
Functional recovery as measured by the modified Rankin scale
Timepoint [4] 330276 0
Assessed at 6 months from enrolment assessed by telephone interview.
Secondary outcome [5] 330277 0
Functional recovery as assessed by the Cerebral Performance Category scale
Timepoint [5] 330277 0
Assessed at 6 months from enrolment assessed by telephone interview.
Secondary outcome [6] 330278 0
Cognitive recovery as assessed using the Montreal Cognitive Assessment (MoCA-blind) questionnaire.
Timepoint [6] 330278 0
Assessed at 6 months from enrolment assessed by telephone interview.
Secondary outcome [7] 330279 0
Quality of life assessed by the EuroQol5D5L scale
Timepoint [7] 330279 0
Assessed at 6 months from enrolment assessed by telephone interview.
Secondary outcome [8] 330280 0
Quality Adjusted Life Years (QALYs)
Timepoint [8] 330280 0
Assessed at 6 months from enrolment assessed comparing changes in EuroQoL5D on two occasions (before hospitalisation and at 6 months from enrolment).

Eligibility
Key inclusion criteria
Adult (greater than or equal to 18 years of age)
Out-of-hospital cardiac arrest of a presumed cardiac or unknown cause
Sustained return of spontaneous circulation - defined as 20 minutes with signs of circulation without the need for chest compressions
Unconscious (FOUR-score motor response of less than 4, not able to obey veral commands after sustained return of spontaenous circulation
Eligible for intensive care without restrictions or limitations
Within less than 180 minutes of return of spontaneous circulation
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unwitnessed cardiac arrest with an initial rhythm of asystole
Temperature on admission of less than 30oC
On extracorporeal membrane oxygenation prior to return of spontaneous circiulation
Obvious or suspected pregnancy
Intracranial bleeding
Severe chronic obstructive pulmonary disorder (COPD) with long-term home oxygen therapy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation will be performed using a secure, web-based, randomisation interface. Randomisation will not be performed until participants fulfil all eligibility criteria and are ready to be assigned to study treatment. Participants will be enrolled in the study by ICU doctors, nurses, and research staff and the assigned intervention will be communicated to the bedside nurse who will implement the study intervention.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A permuted block randomisation method will be used with variable block sizes, stratified by site. The allocation sequence will be generated by the study statistician using computer generated random numbers.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Independent statisticians at Monash University Department of Epidemiology and Preventive Medicine will perform data analysis on an intention-to-treat basis. Baseline and outcome variables will be compared using Chi-square tests for equal proportion, Student’s t-test for normally distributed outcomes and the Mann-Whitney test for any non-parametric data. Multivariate models adjusting for any baseline imbalances and known covariates will be performed using logistic regression. A p-value of 0.05 will be considered to be statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 7167 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 14925 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 295200 0
Government body
Name [1] 295200 0
National Health and Medical Research Council
Address [1] 295200 0
GPO Box 1421
16 Marcus Clarke Street,
Canberra
Australian Capital Territory
2600
Country [1] 295200 0
Australia
Funding source category [2] 297062 0
Government body
Name [2] 297062 0
Irish Health Research Board
Address [2] 297062 0
Health Research Board
Grattan House,
67-72 Lower Mount Street,
Dublin 2, Ireland
Country [2] 297062 0
Ireland
Primary sponsor type
Individual
Name
A/Prof Glenn Eastwood
Address
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country
Australia
Secondary sponsor category [1] 294032 0
None
Name [1] 294032 0
Address [1] 294032 0
Country [1] 294032 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296550 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 296550 0
145 Studley Road
Heidelberg
Victoria 3084
Ethics committee country [1] 296550 0
Australia
Date submitted for ethics approval [1] 296550 0
01/05/2017
Approval date [1] 296550 0
13/07/2017
Ethics approval number [1] 296550 0
HREC/17/Austin/209

Summary
Brief summary
The TAME Cardiac Arrest trial will study the ability of higher carbon dioxide (CO2) levels to reduce brain damage, comparing giving patients ‘normal’ to ‘slightly higher than normal’ blood CO2 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 ICU. This therapy is cost free and, if shown to be effective, will improve thousands of Australian lives, transform clinical practice, and yield major savings.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71262 0
A/Prof Glenn Eastwood
Address 71262 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 71262 0
Australia
Phone 71262 0
+61 3 9496 4835
Fax 71262 0
+61 3 9496 3932
Email 71262 0
glenn.eastwood@austin.org.au
Contact person for public queries
Name 71263 0
A/Prof Glenn Eastwood
Address 71263 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 71263 0
Australia
Phone 71263 0
+ 61 3 9496 4835
Fax 71263 0
+61 3 9496 3932
Email 71263 0
glenn.eastwood@ausitn.org.au
Contact person for scientific queries
Name 71264 0
A/Prof Glenn Eastwood
Address 71264 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 71264 0
Australia
Phone 71264 0
+61 3 9496 5992
Fax 71264 0
+61 3 9496 3932
Email 71264 0
glenn.eastwood@austin.org.au

No information has been provided regarding IPD availability
Summary results
No Results