Target Temperature Management After Cardiac Arrest

NCT01020916 | Completed DMC

• 1 other identifier: TTM-1
• Study Type: interventional
• Target: 950
• Locations: 10 countries
• Sites: 33

Brief Summary

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.

Conditions

Out-of-hospital Cardiac Arrest

Keywords

Induced hypothermia; Mild induced hypothermia; Therapeutic hypothermia; Cardiac arrest; Out-of-hospital cardiac arrest; Mortality; Neurological function; Randomised clinical trial

Outcome Measures

Primary Outcomes (1)

• All-cause mortality

  Maximum follow-up with a minimum of 180 days

Secondary Outcomes (12)

• 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)

  180 days

• Bleeding

  During day 1-7 of intensive care treatment

• Neurological function

  180 days

• Pneumonia

  During day 1-7 of intensive care treatment

• Electrolyte disorders

  During day 1-7 of intensive care treatment

Other Outcomes (3)

• Quality of life

  180 days

• Neurological function including "Complete neurological recovery"*

  180 days

• Neurological function at hospital discharge and best neurological function during follow up period

  Hospital discharge and 1-180 days

Study Arms (2)

Target Temperature 33°C

EXPERIMENTAL

Procedure: Target Temperature 33°C

Target Temperature 36°C

ACTIVE COMPARATOR

Procedure: Target temperature 36°C

Interventions

Target temperature 36°C PROCEDURE

In hospital target temperature management to achieve a core body temperature of 36°C for 24 hours

Target Temperature 36°C

Target Temperature 33°C PROCEDURE

In hospital target temperature management to achieve a core body temperature of 33°C for 24 hours

Target Temperature 33°C

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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#

Sponsors & Collaborators

• Niklas Nielsen: lead
• Scandinavian Critical Care Trials Group: collaborator
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator
• Lund University: collaborator
• The George Institute for Global Health, Australia: collaborator

Study Sites (33)

Liverpool Hospital

Sydney, Australia

Location

North Shore Hospital

Sydney, Australia

Location

St George Hospital

Sydney, Australia

Location

General University Hospital

Prague, Czechia

Location

Copenhagen University Hospital, Rigshospitalet

Copenhagen, DK2100, Denmark

Location

San Martino Hospital

Genova, Italy

Location

Santa Maria degli Angeli Hospital

Pordenone, Italy

Location

Ospedale Universitario di Cattinaria

Trieste, Italy

Location

Centre Hospitalier de Luxembourg

Luxembourg, Luxembourg

Location

Academisch Medisch Centrum, AMC

Amsterdam, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands

Location

Rijnstate Hospital

Arnhem, Netherlands

Location

Leeuwarden Hospital

Leeuwarden, Netherlands

Location

Haukeland University Hospital

Bergen, Norway

Location

Oslo University Hospital, Rikshospitalet

Oslo, Norway

Location

Sahlgrenska University Hospital, Östra

Gothenburg, Sweden

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Helsingborgs Hospital

Helsingborg, 251 87, Sweden

Location

Karlstad Central Hospital

Karlstad, Sweden

Location

Kungälv Hospital

Kungälv, Sweden

Location

Linköping University Hospital

Linköping, Sweden

Location

Skåne University Hospital

Lund, Sweden

Location

Skåne University Hospital

Malmo, Sweden

Location

Vrinnevi Hospital

Norrköping, Sweden

Location

Örebro University Hospital

Örebro, Sweden

Location

Norra Älvsborgs Läns Sjukhus

Trollhättan/Vänersborg, Sweden

Location

University Hospital of Geneva

Geneva, Switzerland

Location

Kantonspital St Gallen

Sankt Gallen, Switzerland

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

Guy's and St Thomas NHS Trust

London, United Kingdom

Location

St Georges' Hospital

London, United Kingdom

Location

Royal Berkshire NHS Foundation Trust

Reading, United Kingdom

Location

Related Publications (34)

• Nielsen N, Friberg H, Gluud C, Herlitz J, Wetterslev J. Hypothermia after cardiac arrest should be further evaluated--a systematic review of randomised trials with meta-analysis and trial sequential analysis. Int J Cardiol. 2011 Sep 15;151(3):333-41. doi: 10.1016/j.ijcard.2010.06.008. Epub 2010 Jul 1.

  PMID: 20591514 BACKGROUND

• Nielsen N, Hovdenes J, Nilsson F, Rubertsson S, Stammet P, Sunde K, Valsson F, Wanscher M, Friberg H; Hypothermia Network. Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand. 2009 Aug;53(7):926-34. doi: 10.1111/j.1399-6576.2009.02021.x. Epub 2009 Jun 22.

  PMID: 19549271 BACKGROUND

• Holgersson J, Meyer MAS, Dankiewicz J, Lilja G, Ullen S, Hassager C, Cronberg T, Wise MP, Belohlavek J, Hovdenes J, Pelosi P, Erlinge D, Schrag C, Smid O, Brunetti I, Rylander C, Young PJ, Saxena M, Aneman A, Cariou A, Callaway C, Eastwood GM, Haenggi M, Joannidis M, Keeble TR, Kirkegaard H, Leithner C, Levin H, Nichol AD, Morgan MPG, Nordberg P, Oddo M, Storm C, Taccone FS, Thomas M, Bro-Jeppesen J, Horn J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher MJ, Friberg H, Nielsen N, Jakobsen JC. Hypothermic versus Normothermic Temperature Control after Cardiac Arrest. NEJM Evid. 2022 Nov;1(11):EVIDoa2200137. doi: 10.1056/EVIDoa2200137. Epub 2022 Jun 15.

  PMID: 38319850 DERIVED

• Beske RP, Obling LER, Bro-Jeppesen J, Nielsen N, Meyer MAS, Kjaergaard J, Johansson PI, Hassager C. The Effect of Targeted Temperature Management on the Metabolome Following Out-of-Hospital Cardiac Arrest. Ther Hypothermia Temp Manag. 2023 Dec;13(4):208-215. doi: 10.1089/ther.2022.0065. Epub 2023 May 23.

  PMID: 37219970 DERIVED

• Arrich J, Schutz N, Oppenauer J, Vendt J, Holzer M, Havel C, Herkner H. Hypothermia for neuroprotection in adults after cardiac arrest. Cochrane Database Syst Rev. 2023 May 22;5(5):CD004128. doi: 10.1002/14651858.CD004128.pub5.

  PMID: 37217440 DERIVED

• Grindegard L, Cronberg T, Backman S, Blennow K, Dankiewicz J, Friberg H, Hassager C, Horn J, Kjaer TW, Kjaergaard J, Kuiper M, Mattsson-Carlgren N, Nielsen N, van Rootselaar AF, Rossetti AO, Stammet P, Ullen S, Zetterberg H, Westhall E, Moseby-Knappe M. Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest: A Post Hoc Analysis of the TTM Trial. Neurology. 2022 Jun 14;98(24):e2487-e2498. doi: 10.1212/WNL.0000000000200335. Epub 2022 Apr 25.

  PMID: 35470143 DERIVED

• Grand J, Kjaergaard J, Hassager C, Moller JE, Bro-Jeppesen J. Comparing Doppler Echocardiography and Thermodilution for Cardiac Output Measurements in a Contemporary Cohort of Comatose Cardiac Arrest Patients Undergoing Targeted Temperature Management. Ther Hypothermia Temp Manag. 2022 Sep;12(3):159-167. doi: 10.1089/ther.2021.0008. Epub 2021 Aug 20.

  PMID: 34415801 DERIVED

• Thomsen JH, Hassager C, Erlinge D, Nielsen N, Lindholm MG, Bro-Jeppesen J, Grand J, Pehrson S, Graff C, Kober LV, Kjaergaard J. Repolarization and ventricular arrhythmia during targeted temperature management post cardiac arrest. Resuscitation. 2021 Sep;166:74-82. doi: 10.1016/j.resuscitation.2021.07.004. Epub 2021 Jul 14.

  PMID: 34271131 DERIVED

• During J, Annborn M, Cronberg T, Dankiewicz J, Devaux Y, Hassager C, Horn J, Kjaergaard J, Kuiper M, Nikoukhah HR, Stammet P, Unden J, Wanscher MJ, Wise M, Friberg H, Nielsen N. Copeptin as a marker of outcome after cardiac arrest: a sub-study of the TTM trial. Crit Care. 2020 Apr 28;24(1):185. doi: 10.1186/s13054-020-02904-8.

  PMID: 32345356 DERIVED

• Rundgren M, Ullen S, Morgan MPG, Glover G, Cranshaw J, Al-Subaie N, Walden A, Joannidis M, Ostermann M, Dankiewicz J, Nielsen N, Wise MP. Renal function after out-of-hospital cardiac arrest; the influence of temperature management and coronary angiography, a post hoc study of the target temperature management trial. Crit Care. 2019 May 8;23(1):163. doi: 10.1186/s13054-019-2390-0.

  PMID: 31068215 DERIVED

• Stammet P, Dankiewicz J, Nielsen N, Fays F, Collignon O, Hassager C, Wanscher M, Unden J, Wetterslev J, Pellis T, Aneman A, Hovdenes J, Wise MP, Gilson G, Erlinge D, Horn J, Cronberg T, Kuiper M, Kjaergaard J, Gasche Y, Devaux Y, Friberg H; Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial investigators. Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 degrees C and 36 degrees C. Crit Care. 2017 Jun 20;21(1):153. doi: 10.1186/s13054-017-1729-7.

  PMID: 28629472 DERIVED

• Wiberg S, Hassager C, Stammet P, Winther-Jensen M, Thomsen JH, Erlinge D, Wanscher M, Nielsen N, Pellis T, Aneman 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.

  PMID: 28099439 DERIVED

• 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. doi: 10.1186/s13054-016-1552-6.

  PMID: 27887653 DERIVED

• 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.

  PMID: 27667713 DERIVED

• 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.

  PMID: 27523954 DERIVED

• Devaux Y, Dankiewicz J, Salgado-Somoza A, Stammet P, Collignon O, Gilje P, Gidlof 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.

  PMID: 27438111 DERIVED

• Bro-Jeppesen J, Kjaergaard J, Stammet P, Wise MP, Hovdenes J, Aneman 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 degrees C or 36 degrees C. Resuscitation. 2016 Jan;98:1-8. doi: 10.1016/j.resuscitation.2015.10.009. Epub 2015 Oct 23.

  PMID: 26525271 DERIVED

• Lilja G, Nilsson G, Nielsen N, Friberg H, Hassager C, Koopmans M, Kuiper M, Martini A, Mellinghoff J, Pelosi P, Wanscher M, Wise MP, Ostman 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.

  PMID: 26433116 DERIVED

• Stammet P, Collignon O, Hassager C, Wise MP, Hovdenes J, Aneman 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 degrees C and 36 degrees C. J Am Coll Cardiol. 2015 May 19;65(19):2104-14. doi: 10.1016/j.jacc.2015.03.538.

  PMID: 25975474 DERIVED

• 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(1):54. doi: 10.1186/s13054-015-0767-2.

  PMID: 25886727 DERIVED

• Cronberg T, Lilja G, Horn J, Kjaergaard J, Wise MP, Pellis T, Hovdenes J, Gasche Y, Aneman A, Stammet P, Erlinge D, Friberg H, Hassager C, Kuiper M, Wanscher M, Bosch F, Cranshaw J, Kleger GR, Persson S, Unden 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 degrees C vs 36 degrees 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.

  PMID: 25844993 DERIVED

• 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.

  PMID: 25789868 DERIVED

• 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.

  PMID: 25756419 DERIVED

• 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 degrees C Versus 36 degrees 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.

  PMID: 25365723 DERIVED

• Bro-Jeppesen J, Hassager C, Wanscher M, Ostergaard M, Nielsen N, Erlinge D, Friberg H, Kober L, Kjaergaard J. Targeted temperature management at 33 degrees C versus 36 degrees 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.

  PMID: 25270900 DERIVED

• Westhall E, Rosen I, Rossetti AO, van Rootselaar AF, Kjaer TW, Horn J, Ullen 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.

  PMID: 25267568 DERIVED

• 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.

  PMID: 25078879 DERIVED

• 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, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206. doi: 10.1056/NEJMoa1310519. Epub 2013 Nov 17.

  PMID: 24237006 DERIVED

• 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.

  PMID: 24188226 DERIVED

• 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, Aneman 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.

  PMID: 24044764 DERIVED

• 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. No abstract available.

  PMID: 23688929 DERIVED

• 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. No abstract available.

  PMID: 23499577 DERIVED

• 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, Langorgen J, Macken L, Martinell L, Martner P, Pellis T, Pelosi P, Petersen P, Persson S, Rundgren M, Saxena M, Svensson R, Stammet P, Thoren A, Unden 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.

  PMID: 22520518 DERIVED

• 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. No abstract available.

  PMID: 21458906 DERIVED

MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Heart Arrest

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Niklas Nielsen, MD, PhD

  Helsingborgs lasarett, Region Skåne, Sweden

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant in Anesthesia and Intensive Care, MD, PhD

Study Record Dates

• First Submitted: November 25, 2009
• First Posted: November 26, 2009
• Study Start: November 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: July 10, 2013

Record last verified: 2013-07

Locations

AU (3); NO (2); NL (4); SE (11); DK (1); CZ (1); IT (3); CH (2); GB (5); LU (1)