Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest

NCT03114033 | Unknown DMC

• 1 other identifier: ANZIC-RC/SB001
• Study Type: interventional
• Target: 1,700
• Locations: 14 countries
• Sites: 52

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.

Conditions

Out-Of-Hospital Cardiac Arrest

Keywords

Cardiac Arrest; Intensive Care Unit; Therapeutic Mild Hypercapnia; Normocapnia; Mortality; Neurological function

Outcome Measures

Primary Outcomes (1)

• Neurological outcome

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

  6 months following enrolment

Secondary Outcomes (8)

• Mortality at intensive care unit discharge

  6 months after randomisation

• Mortality at hospital discharge

  6 months after randomisation

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

  6 months after randomisation

• modified Rankin scale (mRS)

  6 months after randomisation

• Montreal Cognitive Assessment (MoCA-blind)

  6 months after randomisation

Other Outcomes (8)

• Quality Adjust Life Years (QALYs)

  6 months after randomisation

• Health economic evaluation

  6 months after randomisation

• Pneumonia

  Occurring from enrolment until Day 7 while the participant is in the intensive care unit as reported by treating clinicians.

Study Arms (2)

Targeted therapeutic mild hypercapnia

EXPERIMENTAL

Target arterial carbon dioxide range of 50-55 mmHg for 24 hours following randomisation

Other: Targeted therapeutic mild hypercapnia

Targeted normocapnia (Standard care)

ACTIVE COMPARATOR

Target arterial carbon dioxide range of 35-45 mmHg for 24 hours following randomisation

Other: Targeted normocapnia (Standard care)

Interventions

Targeted therapeutic mild hypercapnia OTHER

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 therapeutic mild hypercapnia

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.

Targeted normocapnia (Standard care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Australian and New Zealand Intensive Care Research Centre: lead
• National Health and Medical Research Council, Australia: collaborator
• Health Research Board, Ireland: collaborator

Study Sites (52)

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Nepean Hospital

Penrith, New South Wales, 2750, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

Royal Darwin Hospital

Tiwi, Northern Territory, 0810, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

Nambour Hospital

Sunshine Coast, Queensland, 4560, Australia

Location

Sunshine Coast University Hospital

Sunshine Coast, Queensland, 4575, Australia

Location

Flinders Medical Centre

Adelaide, South Australia, 3929, Australia

Location

Ballarat Base Hospital

Ballarat, Victoria, 3350, Australia

Location

The Northern Hospital

Epping, Victoria, 3076, Australia

Location

University Hospital Geelong

Geelong, Victoria, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

Footscray Hospital-Western Health

Melbourne, Victoria, 3011, Australia

Location

Sunshine Hospital-Western Health

Melbourne, Victoria, 3021, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Austin Health

Melbourne, Victoria, 3084, Australia

Location

Cliniques Universitaires de Bruxelles Hospital Erasme

Brussels, 1070, Belgium

Location

Ziekenhuis Oost-Limburg AV

Genk, 3600, Belgium

Location

University Hospital Ghent

Ghent, 9000, Belgium

Location

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

CHRU Jean Minjoz Besancon

Besançon, Franche Comte, 25000, France

Location

St. Vincent's University Hospital

Dublin, Dublin 4, Ireland

Location

St. James's Hospital

Dublin, Dublin 8, Ireland

Location

Beaumont Hospital

Dublin, Dublin 9, Ireland

Location

University Hospital Galway

Galway, H91 YR71, Ireland

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Amsterdam University Medical Centre

Amsterdam, 1105, Netherlands

Location

Auckland City Hospital CVICU

Grafton, Auckland, 1023, New Zealand

Location

Auckland City Hospital DCCM

Grafton, Auckland, 1023, New Zealand

Location

Middlemore Hospital

Otahuhu, Auckland, 2025, New Zealand

Location

Christchurch Hospital

Riccarton, Christchurch, 8011, New Zealand

Location

Wellington Regional Hospital

Newtown, Wellington Region, 6021, New Zealand

Location

North Shore Hospital

Auckland, 0622, New Zealand

Location

Rotorua Hospital

Rotorua, 3010, New Zealand

Location

Oslo University Hospital - Ullevål

Oslo, 0450, Norway

Location

King Abdulaziz Medical City

Riyadh, 14611, Saudi Arabia

Location

University Medical Centre Maribor

Maribor, 2000, Slovenia

Location

Skane Region-Helsingborg

Helsingborg, 25437, Sweden

Location

Skane Region Malmö

Malmo, 21421, Sweden

Location

Queen Alexandra Hospital Portsmouth

Cosham, Portsmouth, PO6 3LY, United Kingdom

Location

Royal Victoria Hospital Belfast

Belfast, BT12 6BA, United Kingdom

Location

Birmingham University Hospital

Birmingham, B15 2TH, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Bristol Royal Infirmary

Bristol, BS2 8HW, United Kingdom

Location

University Hospital Wales

Cardiff, CF14 4XW, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Royal Berkshire Hospital

Reading, RG1 5AN, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 27060535 RESULT

• Melberg MB, Rootwelt SD, Flaa A, Andersen GO, Sunde K, Eastwood G, 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. 2025 Nov 24:S0012-3692(25)05796-4. doi: 10.1016/j.chest.2025.11.017. Online ahead of print.

  PMID: 41297587 DERIVED

• 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.

  PMID: 38936652 DERIVED

• 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.

  PMID: 38046686 DERIVED

• 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.

  PMID: 37318140 DERIVED

MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Heart Arrest

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Glenn M Eastwood, RN, PhD

  Monash University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A Randomised, Parallel Groups, Assessor Blinded, Clinical Trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel assignment

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: April 14, 2017
• Study Start: February 15, 2018
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: April 20, 2022

Record last verified: 2022-04

Locations

IT (1); AU (20); FI (1); NL (1); NO (1); NZ (7); SA (1); SL (1); SE (2); GB (8); BE (3); DK (1); IE (4); FR (1)