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Out-Of-Hospital Cardiac ArrestTAMENCT03114033

Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest

A study testing Targeted therapeutic mild hypercapnia in people with Out-Of-Hospital Cardiac Arrest, run by Australian and New Zealand Intensive Care Research Centre at 52 sites in 14 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Out-Of-Hospital Cardiac Arrest
What is being tested?
Targeted therapeutic mild hypercapnia
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,700 participants
Where
52 sitesin 14 countries
Study dates
15 Feb 2018to Dec 2022
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

52 sites in 14 countries.

52 sites in 14 countries

Australia20 sites
  • Flinders Medical Centre

    Adelaide, South Australia, 3929

  • Ballarat Base Hospital

    Ballarat, Victoria, 3350

  • Royal Brisbane and Women's Hospital

    Brisbane, Queensland, 4029

  • Princess Alexandra Hospital

    Brisbane, Queensland, 4102

  • Prince Charles Hospital

    Chermside, Queensland, 4032

  • St Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • The Northern Hospital

    Epping, Victoria, 3076

  • University Hospital Geelong

    Geelong, Victoria

  • Alfred Health

    Melbourne, Victoria, 3004

  • Footscray Hospital-Western Health

    Melbourne, Victoria, 3011

  • Sunshine Hospital-Western Health

    Melbourne, Victoria, 3021

  • Royal Melbourne Hospital

    Melbourne, Victoria, 3050

  • Austin Health

    Melbourne, Victoria, 3084

  • Nepean Hospital

    Penrith, New South Wales, 2750

  • Gold Coast University Hospital

    Southport, Queensland, 4215

  • Royal North Shore Hospital

    St Leonards, New South Wales, 2065

  • Nambour Hospital

    Sunshine Coast, Queensland, 4560

  • Sunshine Coast University Hospital

    Sunshine Coast, Queensland, 4575

  • Royal Darwin Hospital

    Tiwi, Northern Territory, 0810

  • Wollongong Hospital

    Wollongong, New South Wales, 2500

Other trials in Australia

United Kingdom8 sites
  • Royal Victoria Hospital Belfast

    Belfast, BT12 6BA

  • Birmingham University Hospital

    Birmingham, B15 2TH

  • Royal Bournemouth Hospital

    Bournemouth, BH7 7DW

  • Bristol Royal Infirmary

    Bristol, BS2 8HW

  • University Hospital Wales

    Cardiff, CF14 4XW

  • Queen Alexandra Hospital Portsmouth

    Cosham, Portsmouth, PO6 3LY

  • Manchester Royal Infirmary

    Manchester, M13 9WL

  • Royal Berkshire Hospital

    Reading, RG1 5AN

Other trials in United Kingdom

New Zealand7 sites
  • North Shore Hospital

    Auckland, 0622

  • Auckland City Hospital CVICU

    Grafton, Auckland, 1023

  • Auckland City Hospital DCCM

    Grafton, Auckland, 1023

  • Wellington Regional Hospital

    Newtown, Wellington Region, 6021

  • Middlemore Hospital

    Otahuhu, Auckland, 2025

  • Christchurch Hospital

    Riccarton, Christchurch, 8011

  • Rotorua Hospital

    Rotorua, 3010

Other trials in New Zealand

Ireland4 sites
  • St. Vincent's University Hospital

    Dublin, Dublin 4

  • St. James's Hospital

    Dublin, Dublin 8

  • Beaumont Hospital

    Dublin, Dublin 9

  • University Hospital Galway

    Galway, H91 YR71

Other trials in Ireland

Belgium3 sites
  • Cliniques Universitaires de Bruxelles Hospital Erasme

    Brussels, 1070

  • Ziekenhuis Oost-Limburg AV

    Genk, 3600

  • University Hospital Ghent

    Ghent, 9000

Other trials in Belgium

Sweden2 sites
  • Skane Region-Helsingborg

    Helsingborg, 25437

  • Skane Region Malmö

    Malmö, 21421

Other trials in Sweden

Denmark1 site
  • Aarhus University Hospital

    Aarhus, 8200

Other trials in Denmark

Finland1 site
  • Helsinki University Central Hospital

    Helsinki, 00029

Other trials in Finland

France1 site
  • CHRU Jean Minjoz Besancon

    Besançon, Franche Comte, 25000

Other trials in France

Italy1 site
  • Ospedale San Raffaele

    Milan, 20132

Other trials in Italy

Netherlands1 site
  • Amsterdam University Medical Centre

    Amsterdam, 1105

Other trials in Netherlands

Norway1 site
  • Oslo University Hospital - Ullevål

    Oslo, 0450

Other trials in Norway

Saudi Arabia1 site
  • King Abdulaziz Medical City

    Riyadh, 14611

Other trials in Saudi Arabia

Slovenia1 site
  • University Medical Centre Maribor

    Maribor, 2000

Other trials in Slovenia

About this study

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

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.

Read the 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.

Being tested
Targeted therapeutic mild hypercapnia, Targeted normocapnia (Standard care)
Keywords
Cardiac Arrest, Intensive Care Unit, Therapeutic Mild Hypercapnia, Normocapnia, Mortality, Neurological function
Medical subject headings
Out-of-Hospital Cardiac Arrest, Heart Arrest

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Targeted therapeutic mild hypercapniaOther

    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

  • Targeted normocapnia (Standard care)Other

    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.

Study groups in NCT03114033
Study groupRoleWhat they receive
Targeted therapeutic mild hypercapniaExperimentalTarget arterial carbon dioxide range of 50-55 mmHg for 24 hours following randomisation
Receives: Other: Targeted therapeutic mild hypercapnia
Targeted normocapnia (Standard care)Active comparatorTarget arterial carbon dioxide range of 35-45 mmHg for 24 hours following randomisation
Receives: Other: Targeted normocapnia (Standard care)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Neurological outcome

    Proportion of patients with a favourable (score ≥5) neurological outcome as assessed using the Glasgow Outcomes Score Extended (GOSE) method.

    Measured: 6 months following enrolment

Secondary outcomes (8)
  1. Mortality at intensive care unit discharge

    Mortality at intensive care unit discharge

    Measured: 6 months after randomisation

  2. Mortality at hospital discharge

    Mortality at hospital discharge

    Measured: 6 months after randomisation

  3. Health-related Quality of Life (EQ-5D-5L)

    Health-related Quality of Life (EQ-5D-5L) at 6 months

    Measured: 6 months after randomisation

  4. modified Rankin scale (mRS)

    modified Rankin scale (mRS) with favourable score of equal to or less than 3

    Measured: 6 months after randomisation

  5. Montreal Cognitive Assessment (MoCA-blind)

    Montreal Cognitive Assessment (MoCA-blind) at 6 months

    Measured: 6 months after randomisation

  6. Mortality at 6 months

    Mortality at 6 months

    Measured: 6 months after randomisation

  7. Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest (IQCODE)

    IQCODE

    Measured: 6 months after randomisation

  8. Symbol Digit Modality Test

    SDMT at 6 months

    Measured: 6 months after randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2017
  2. Study start15 Feb 2018
  3. Primary completionDec 2022 (estimated)
  4. Study completionDec 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel assignment
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
1,700 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03114033
Sponsor's protocol ID
ANZIC-RC/SB001
Acronym
TAME
Status last verified
Apr 2022
First submitted
11 Apr 2017
Last updated
20 Apr 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Eastwood GM, Schneider AG, Suzuki S, Peck L, Young H, Tanaka A, Martensson J, Warrillow S, McGuinness S, Parke R, Gilder E, Mccarthy L, Galt P, Taori G, Eliott S, Lamac T, Bailey M, Harley N, Barge D, Hodgson CL, Morganti-Kossmann MC, Pebay A, Conquest A, Archer JS, Bernard S, Stub D, Hart GK, Bellomo R. Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial). Resuscitation. 2016 Jul;104:83-90. doi: 10.1016/j.resuscitation.2016.03.023. Epub 2016 Apr 7.

    PubMed 27060535
  • Melberg MB, Rootwelt SD, Flaa A, Andersen GO, Sunde K, Eastwood G, Bellomo R, Olasveengen TM, Qvigstad E. The Effects of Targeted Mild Hypercapnia on Right Ventricular Function After Out-of-Hospital Cardiac Arrest: A Substudy of the Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest Trial. Chest. 2026 Jul;170(1):105-117. doi: 10.1016/j.chest.2025.11.017. Epub 2025 Nov 24.

    PubMed 41297587
  • Lee YY, Eastwood G, Bailey MJ, Bellomo R, Nichol AD, Parke RL, McGuinness S, Bernard S, Arabi YM, Capellier G, Chia YW, Grejs A, Haenggi M, Kutsogiannis D, Landoni G, Markota A, Nielsen N, Olasveengen T, Skrifvars MB, Taccone F, Wise MP, Higgins AM; TAME Study Investigators. The cost-effectiveness of mild hypercapnia after out-of-hospital cardiac arrest: a health economic evaluation alongside the TAME study. Resuscitation. 2025 Dec;217:110878. doi: 10.1016/j.resuscitation.2025.110878. Epub 2025 Oct 30.

    PubMed 41176021
  • Melberg MB, Flaa A, Andersen GO, Sunde K, Bellomo R, Eastwood G, Olasveengen TM, Qvigstad E. Effects of mild hypercapnia on myocardial injury after out-of-hospital cardiac arrest. A sub-study of the TAME trial. Resuscitation. 2024 Aug;201:110295. doi: 10.1016/j.resuscitation.2024.110295. Epub 2024 Jun 25.

    PubMed 38936652
  • Nichol A, Bellomo R, Ady B, Nielsen N, Hodgson C, Parke R, McGuinness S, Skrifvars M, Stub D, Bernard S, Taccone F, Archer J, Neto AS, Trapani T, Ainscough K, Hunt A, Kutsogiannis J, Eastwood GM. Protocol summary and statistical analysis plan for the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial. Crit Care Resusc. 2023 Oct 18;23(4):374-385. doi: 10.51893/2021.4.OA2. eCollection 2021 Dec 6.

    PubMed 38046686
  • Eastwood G, Nichol AD, Hodgson C, Parke RL, McGuinness S, Nielsen N, Bernard S, Skrifvars MB, Stub D, Taccone FS, Archer J, Kutsogiannis D, Dankiewicz J, Lilja G, Cronberg T, Kirkegaard H, Capellier G, Landoni G, Horn J, Olasveengen T, Arabi Y, Chia YW, Markota A, Haenggi M, Wise MP, Grejs AM, Christensen S, Munk-Andersen H, Granfeldt A, Andersen GO, Qvigstad E, Flaa A, Thomas M, Sweet K, Bewley J, Backlund M, Tiainen M, Iten M, Levis A, Peck L, Walsham J, Deane A, Ghosh A, Annoni F, Chen Y, Knight D, Lesona E, Tlayjeh H, Svensek F, McGuigan PJ, Cole J, Pogson D, Hilty MP, During JP, Bailey MJ, Paul E, Ady B, Ainscough K, Hunt A, Monahan S, Trapani T, Fahey C, Bellomo R; TAME Study Investigators. Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest. N Engl J Med. 2023 Jul 6;389(1):45-57. doi: 10.1056/NEJMoa2214552. Epub 2023 Jun 15.

    PubMed 37318140

Questions about this trial

What is this clinical trial studying?

A study testing Targeted therapeutic mild hypercapnia in people with Out-Of-Hospital Cardiac Arrest, run by Australian and New Zealand Intensive Care Research Centre at 52 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 20 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in Australia, United Kingdom, New Zealand, Ireland, Belgium and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Neurological outcome (time frame: 6 months following enrolment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03114033, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2022; AzTrials last refreshed its copy on 6 Nov 2026.

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