We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Target Temperature Management After Cardiac Arrest (TTM)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01020916
First Posted: November 26, 2009
Last Update Posted: July 10, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Scandinavian Critical Care Trials Group
Copenhagen Trial Unit, Center for Clinical Intervention Research
Lund University
The George Institute for Global Health, Australia
Information provided by (Responsible Party):
Niklas Nielsen, Helsingborgs Hospital
  Purpose
Experimental studies and previous clinical trials suggest an improvement in mortality and neurological function with hypothermia after cardiac arrest. However, the accrued evidence is inconclusive and associated with risks of systematic error, design error and random error. Elevated body temperature after cardiac arrest is associated with a worse outcome. Previous trials did not treat elevated body temperature in the control groups. The optimal target temperature for post-resuscitation care is not known. The primary purpose with the TTM-trial is to evaluate if there are differences in all-cause mortality, neurological function and adverse events between a target temperature management at 33°C and 36°C for 24 hours following return of spontaneous circulation after cardiac arrest.

Condition Intervention
Out-of-hospital Cardiac Arrest Procedure: Target temperature 36°C Procedure: Target Temperature 33°C

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Target Temperature Management 33°C Versus 36°C After Out-of-hospital Cardiac Arrest, a Randomised, Parallel Groups, Assessor Blinded Clinical Trial

Resource links provided by NLM:


Further study details as provided by Niklas Nielsen, Helsingborgs Hospital:

Primary Outcome Measures:
  • All-cause mortality [ Time Frame: Maximum follow-up with a minimum of 180 days ]

Secondary Outcome Measures:
  • Composite outcome of all-cause mortality and poor neurological function (CPC 3 and 4) and composite outcome of all-cause mortality and poor neurological function (modified Rankin Scale 4 and 5) [ Time Frame: 180 days ]
  • Bleeding [ Time Frame: During day 1-7 of intensive care treatment ]
  • Neurological function [ Time Frame: 180 days ]
    Cerebral Performance Category, Modified Rankin Scale

  • Pneumonia [ Time Frame: During day 1-7 of intensive care treatment ]
  • Electrolyte disorders [ Time Frame: During day 1-7 of intensive care treatment ]
  • Hyperglycaemia > 10 mmol/l [ Time Frame: During day 1-7 of intensive care treatment ]
  • Hypoglycemia < 3mmol/l [ Time Frame: During day 1-7 of intensive care treatment ]
  • Cardiac arrhythmia [ Time Frame: During day 1-7 of intensive care treatment ]
  • The need for renal replacement therapy [ Time Frame: During day 1-7 of intensive care treatment ]
  • Landmark all-cause mortality [ Time Frame: 180 days ]
  • Cerebral Performance Category (CPC) [ Time Frame: 180 days ]
    CPC 1,2,3,4,5

  • Modified Rankin Scale (mRS) [ Time Frame: 180 days ]
    mRS 1,2,3,4,5,6


Other Outcome Measures:
  • Quality of life [ Time Frame: 180 days ]
    SF-36

  • Neurological function including "Complete neurological recovery"* [ Time Frame: 180 days ]

    Mini mental state exam (MMSE), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and two questions*

    *Survivors with complete recovery defined by: MMSE ≥27 (or ≥19 on MMSE-Adult Lifestyle Functioning Interview by telephone interview), modified IQCODE ≤78, answer "No" to question 1a or "No" to question 1b, answer "Yes" to question 2.

    1a. "In the last 2 weeks, did you require help from another person for your every day activities?" (If yes, 1b. "Is this a new situation following the heart arrest?") and 2. "Do you feel that you have made a complete mental recovery after your heart arrest?


  • Neurological function at hospital discharge and best neurological function during follow up period [ Time Frame: Hospital discharge and 1-180 days ]
    CPC at hospital discharge and best CPC during the first 180 days after cardiac arrest


Estimated Enrollment: 950
Study Start Date: November 2010
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Target Temperature 33°C Procedure: Target Temperature 33°C
In hospital target temperature management to achieve a core body temperature of 33°C for 24 hours
Active Comparator: Target Temperature 36°C Procedure: Target temperature 36°C
In hospital target temperature management to achieve a core body temperature of 36°C for 24 hours

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Age ≥ 18 years old
  • Out-of-hospital cardiac arrest (OHCA) of presumed cardiac cause
  • Return of spontaneous circulation (ROSC)
  • Unconsciousness (Glasgow Coma Score < 8) (patients not able to obey verbal commands)after sustained ROSC

Exclusion Criteria:

  • In-hospital cardiac arrest
  • OHCA of presumed non-cardiac cause, e.g. after trauma or dissection/rupture of major artery OR Cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging).
  • Known bleeding diathesis (medically induced coagulopathy (e.g warfarin, clopidogrel) does not exclude the patient).
  • Suspected or confirmed acute intracranial bleeding
  • Suspected or confirmed acute stroke
  • Unwitnessed asystole
  • Known limitations in therapy and Do Not Resuscitate-order
  • Known disease making 180 days survival unlikely
  • Known pre-arrest CPC 3 or 4
  • Temperature < 30°C on admission
  • > 4 hours (240 minutes) from ROSC to screening
  • Systolic blood pressure < 80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra aortic balloon pump#

    • If the systolic blood pressure (SBP) is recovering during the inclusion window (220 minutes) the patient can be included.
  Contacts and Locations
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): NCT01020916


  Show 33 Study Locations
Sponsors and Collaborators
Niklas Nielsen
Scandinavian Critical Care Trials Group
Copenhagen Trial Unit, Center for Clinical Intervention Research
Lund University
The George Institute for Global Health, Australia
Investigators
Study Chair: Niklas Nielsen, MD, PhD Helsingborgs lasarett, Region Skåne, Sweden
Principal Investigator: Janneke Horn, MD, PhD Academisch Medisch Centrum, Amsterdam, the Netherlands
Principal Investigator: Hans Friberg, MD, PhD Lund University Hospital, Lund, Sweden
Principal Investigator: Tobias Cronberg, MD, PhD Lund University Hospital, Lund, Sweden
Principal Investigator: Michael Wanscher, MD, PhD Copenhagen University Hospital, Copenhagen, Denmark
Principal Investigator: Christian Hassager, MD, DMSc Copenhagen University Hospital, Copenhagen, Denmark
Principal Investigator: Jesper Kjaergaard, MD, PhD Copenhagen University Hospital, Copenhagen, Denmark
Principal Investigator: Jan Hovdenes, MD, PhD Oslo University Hospital, Oslo, Norway
Principal Investigator: Pascal Stammet, MD Centre Hospitalier du Luxembourg
Principal Investigator: Yvan Gasche, MD, PhD Geneva University Hospital, Geneva, Switzerland
Principal Investigator: Thomas Pellis, MD, PhD Santa Maria degli Angeli Hospital, Pordenone, Italy
Principal Investigator: Matt Wise, MD, DPhil University Hospital of Wales, Cardiff, UK
Principal Investigator: Anders Åneman, MD, PhD Liverpool Hospital, Sydney, Australia
Principal Investigator: Jørn Wetterslev, MD, PhD Copenhagen Trial Unit, Copenhagen University Hospital, Copenhagen, Denmark
Principal Investigator: Michael Kuiper, MD, PhD Leeuwarden Hospital, Leeuwarden, the Netherlands
Principal Investigator: David Erlinge, MD, PhD Lund University Hospital, Lund, Sweden
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Wiberg S, Hassager C, Stammet P, Winther-Jensen M, Thomsen JH, Erlinge D, Wanscher M, Nielsen N, Pellis T, Åneman A, Friberg H, Hovdenes J, Horn J, Wetterslev J, Bro-Jeppesen J, Wise MP, Kuiper M, Cronberg T, Gasche Y, Devaux Y, Kjaergaard J. Single versus Serial Measurements of Neuron-Specific Enolase and Prediction of Poor Neurological Outcome in Persistently Unconscious Patients after Out-Of-Hospital Cardiac Arrest - A TTM-Trial Substudy. PLoS One. 2017 Jan 18;12(1):e0168894. doi: 10.1371/journal.pone.0168894. eCollection 2017.
Glover GW, Thomas RM, Vamvakas G, Al-Subaie N, Cranshaw J, Walden A, Wise MP, Ostermann M, Thomas-Jones E, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wetterslev J, Friberg H, Nielsen N. Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest - an analysis of the TTM trial data. Crit Care. 2016 Nov 26;20(1):381.
Gilje P, Koul S, Thomsen JH, Devaux Y, Friberg H, Kuiper M, Horn J, Nielsen N, Pellis T, Stammet P, Wise MP, Kjaergaard J, Hassager C, Erlinge D; TTM study group. High-sensitivity troponin-T as a prognostic marker after out-of-hospital cardiac arrest - A targeted temperature management (TTM) trial substudy. Resuscitation. 2016 Oct;107:156-61. doi: 10.1016/j.resuscitation.2016.06.024.
Bro-Jeppesen J, Johansson PI, Hassager C, Wanscher M, Ostrowski SR, Bjerre M, Kjaergaard J. Endothelial activation/injury and associations with severity of post-cardiac arrest syndrome and mortality after out-of-hospital cardiac arrest. Resuscitation. 2016 Oct;107:71-9. doi: 10.1016/j.resuscitation.2016.08.006. Epub 2016 Aug 11.
Devaux Y, Dankiewicz J, Salgado-Somoza A, Stammet P, Collignon O, Gilje P, Gidlöf O, Zhang L, Vausort M, Hassager C, Wise MP, Kuiper M, Friberg H, Cronberg T, Erlinge D, Nielsen N; for Target Temperature Management After Cardiac Arrest Trial Investigators. Association of Circulating MicroRNA-124-3p Levels With Outcomes After Out-of-Hospital Cardiac Arrest: A Substudy of a Randomized Clinical Trial. JAMA Cardiol. 2016 Jun 1;1(3):305-13. doi: 10.1001/jamacardio.2016.0480.
Bro-Jeppesen J, Kjaergaard J, Stammet P, Wise MP, Hovdenes J, Åneman A, Horn J, Devaux Y, Erlinge D, Gasche Y, Wanscher M, Cronberg T, Friberg H, Wetterslev J, Pellis T, Kuiper M, Nielsen N, Hassager C; TTM-Trial Investigators. Predictive value of interleukin-6 in post-cardiac arrest patients treated with targeted temperature management at 33 °C or 36 °C. Resuscitation. 2016 Jan;98:1-8. doi: 10.1016/j.resuscitation.2015.10.009. Epub 2015 Oct 23.
Lilja G, Nilsson G, Nielsen N, Friberg H, Hassager C, Koopmans M, Kuiper M, Martini A, Mellinghoff J, Pelosi P, Wanscher M, Wise MP, Östman I, Cronberg T. Anxiety and depression among out-of-hospital cardiac arrest survivors. Resuscitation. 2015 Dec;97:68-75. doi: 10.1016/j.resuscitation.2015.09.389. Epub 2015 Oct 9.
Stammet P, Collignon O, Hassager C, Wise MP, Hovdenes J, Åneman A, Horn J, Devaux Y, Erlinge D, Kjaergaard J, Gasche Y, Wanscher M, Cronberg T, Friberg H, Wetterslev J, Pellis T, Kuiper M, Gilson G, Nielsen N; TTM-Trial Investigators. Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33°C and 36°C. J Am Coll Cardiol. 2015 May 19;65(19):2104-14. doi: 10.1016/j.jacc.2015.03.538. Erratum in: J Am Coll Cardiol. 2015 Aug 25;66(8):983.
Devaux Y, Stammet P, Friberg H, Hassager C, Kuiper MA, Wise MP, Nielsen N; Biomarker subcommittee of TTM trial (Target Temperature Management After Cardiac Arrest, NCT01020916). MicroRNAs: new biomarkers and therapeutic targets after cardiac arrest? Crit Care. 2015 Feb 11;19:54. doi: 10.1186/s13054-015-0767-2. Review.
Cronberg T, Lilja G, Horn J, Kjaergaard J, Wise MP, Pellis T, Hovdenes J, Gasche Y, Åneman A, Stammet P, Erlinge D, Friberg H, Hassager C, Kuiper M, Wanscher M, Bosch F, Cranshaw J, Kleger GR, Persson S, Undén J, Walden A, Winkel P, Wetterslev J, Nielsen N; TTM Trial Investigators. Neurologic Function and Health-Related Quality of Life in Patients Following Targeted Temperature Management at 33°C vs 36°C After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA Neurol. 2015 Jun;72(6):634-41. doi: 10.1001/jamaneurol.2015.0169.
Johansson PI, Bro-Jeppesen J, Kjaergaard J, Wanscher M, Hassager C, Ostrowski SR. Sympathoadrenal activation and endothelial damage are inter correlated and predict increased mortality in patients resuscitated after out-of-hospital cardiac arrest. a post Hoc sub-study of patients from the TTM-trial. PLoS One. 2015 Mar 19;10(3):e0120914. doi: 10.1371/journal.pone.0120914. eCollection 2015.
Bro-Jeppesen J, Kjaergaard J, Wanscher M, Nielsen N, Friberg H, Bjerre M, Hassager C. Systemic Inflammatory Response and Potential Prognostic Implications After Out-of-Hospital Cardiac Arrest: A Substudy of the Target Temperature Management Trial. Crit Care Med. 2015 Jun;43(6):1223-32. doi: 10.1097/CCM.0000000000000937.
Bro-Jeppesen J, Annborn M, Hassager C, Wise MP, Pelosi P, Nielsen N, Erlinge D, Wanscher M, Friberg H, Kjaergaard J; TTM Investigators. Hemodynamics and vasopressor support during targeted temperature management at 33°C Versus 36°C after out-of-hospital cardiac arrest: a post hoc study of the target temperature management trial*. Crit Care Med. 2015 Feb;43(2):318-27. doi: 10.1097/CCM.0000000000000691.
Bro-Jeppesen J, Hassager C, Wanscher M, Østergaard M, Nielsen N, Erlinge D, Friberg H, Køber L, Kjaergaard J. Targeted temperature management at 33°C versus 36°C and impact on systemic vascular resistance and myocardial function after out-of-hospital cardiac arrest: a sub-study of the Target Temperature Management Trial. Circ Cardiovasc Interv. 2014 Oct;7(5):663-72. doi: 10.1161/CIRCINTERVENTIONS.114.001556. Epub 2014 Sep 30.
Westhall E, Rosén I, Rossetti AO, van Rootselaar AF, Kjaer TW, Horn J, Ullén S, Friberg H, Nielsen N, Cronberg T. Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design. BMC Neurol. 2014 Aug 16;14:159. doi: 10.1186/s12883-014-0159-2.
Beurskens CJ, Horn J, de Boer AM, Schultz MJ, van Leeuwen EM, Vroom MB, Juffermans NP. Cardiac arrest patients have an impaired immune response, which is not influenced by induced hypothermia. Crit Care. 2014 Jul 30;18(4):R162. doi: 10.1186/cc14002.
Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206. doi: 10.1056/NEJMoa1310519. Epub 2013 Nov 17.
Ferreira Da Silva IR, Frontera JA. Targeted temperature management in survivors of cardiac arrest. Cardiol Clin. 2013 Nov;31(4):637-55, ix. doi: 10.1016/j.ccl.2013.07.010. Review.
Nielsen N, Winkel P, Cronberg T, Erlinge D, Friberg H, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Wetterslev J. Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial. Trials. 2013 Sep 17;14:300. doi: 10.1186/1745-6215-14-300.
Cronberg T, Nielsen N. Fever after therapeutic hypothermia - does rebound pyrexia matter? Resuscitation. 2013 Aug;84(8):1011-2. doi: 10.1016/j.resuscitation.2013.05.006. Epub 2013 May 17.
Nielsen N, Friberg H. Can we conclude anything yet about the effect of hypothermia for patients arresting in-hospital? Resuscitation. 2013 May;84(5):535-6. doi: 10.1016/j.resuscitation.2013.02.009. Epub 2013 Mar 13.
Nielsen N, Wetterslev J, al-Subaie N, Andersson B, Bro-Jeppesen J, Bishop G, Brunetti I, Cranshaw J, Cronberg T, Edqvist K, Erlinge D, Gasche Y, Glover G, Hassager C, Horn J, Hovdenes J, Johnsson J, Kjaergaard J, Kuiper M, Langørgen J, Macken L, Martinell L, Martner P, Pellis T, Pelosi P, Petersen P, Persson S, Rundgren M, Saxena M, Svensson R, Stammet P, Thorén A, Undén J, Walden A, Wallskog J, Wanscher M, Wise MP, Wyon N, Aneman A, Friberg H. Target Temperature Management after out-of-hospital cardiac arrest--a randomized, parallel-group, assessor-blinded clinical trial--rationale and design. Am Heart J. 2012 Apr;163(4):541-8. doi: 10.1016/j.ahj.2012.01.013.
Nielsen N, Friberg H. Insights from the evidence evaluation process--do we have the answers for therapeutic hypothermia? Resuscitation. 2011 May;82(5):501-2. doi: 10.1016/j.resuscitation.2011.02.041. Epub 2011 Mar 10.

Responsible Party: Niklas Nielsen, Consultant in Anesthesia and Intensive Care, MD, PhD, Helsingborgs Hospital
ClinicalTrials.gov Identifier: NCT01020916     History of Changes
Other Study ID Numbers: TTM-1
First Submitted: November 25, 2009
First Posted: November 26, 2009
Last Update Posted: July 10, 2013
Last Verified: July 2013

Keywords provided by Niklas Nielsen, Helsingborgs Hospital:
Induced hypothermia
Mild induced hypothermia
Therapeutic hypothermia
Cardiac arrest
Out-of-hospital cardiac arrest
Mortality
Neurological function
Randomised clinical trial

Additional relevant MeSH terms:
Heart Arrest
Out-of-Hospital Cardiac Arrest
Heart Diseases
Cardiovascular Diseases


To Top