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Target Temperature Management After Cardiac Arrest (TTM)

This study has been completed.
Sponsor:
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
ClinicalTrials.gov Identifier:
NCT01020916
First received: November 25, 2009
Last updated: July 8, 2013
Last verified: July 2013
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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 Helsingborgs Hospital:

Primary Outcome Measures:
  • All-cause mortality [ Time Frame: Maximum follow-up with a minimum of 180 days ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • Bleeding [ Time Frame: During day 1-7 of intensive care treatment ] [ Designated as safety issue: Yes ]
  • Neurological function [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Cerebral Performance Category, Modified Rankin Scale

  • Pneumonia [ Time Frame: During day 1-7 of intensive care treatment ] [ Designated as safety issue: Yes ]
  • Electrolyte disorders [ Time Frame: During day 1-7 of intensive care treatment ] [ Designated as safety issue: Yes ]
  • Hyperglycaemia > 10 mmol/l [ Time Frame: During day 1-7 of intensive care treatment ] [ Designated as safety issue: Yes ]
  • Hypoglycemia < 3mmol/l [ Time Frame: During day 1-7 of intensive care treatment ] [ Designated as safety issue: Yes ]
  • Cardiac arrhythmia [ Time Frame: During day 1-7 of intensive care treatment ] [ Designated as safety issue: Yes ]
  • The need for renal replacement therapy [ Time Frame: During day 1-7 of intensive care treatment ] [ Designated as safety issue: Yes ]
  • Landmark all-cause mortality [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • Cerebral Performance Category (CPC) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    CPC 1,2,3,4,5

  • Modified Rankin Scale (mRS) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    mRS 1,2,3,4,5,6


Other Outcome Measures:
  • Quality of life [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    SF-36

  • Neurological function including "Complete neurological recovery"* [ Time Frame: 180 days ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01020916

  Hide Study Locations
Locations
Australia
Liverpool Hospital
Sydney, Australia
North Shore Hospital
Sydney, Australia
St George Hospital
Sydney, Australia
Czech Republic
General University Hospital
Prague, Czech Republic
Denmark
Copenhagen University Hospital, Rigshospitalet
Copenhagen, Denmark, DK2100
Italy
San Martino Hospital
Genova, Italy
Santa Maria degli Angeli Hospital
Pordenone, Italy
Ospedale Universitario di Cattinaria
Trieste, Italy
Luxembourg
Centre Hospitalier de Luxembourg
Luxembourg, Luxembourg
Netherlands
Academisch Medisch Centrum, AMC
Amsterdam, Netherlands
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands
Rijnstate Hospital
Arnhem, Netherlands
Leeuwarden Hospital
Leeuwarden, Netherlands
Norway
Haukeland University Hospital
Bergen, Norway
Oslo University Hospital, Rikshospitalet
Oslo, Norway
Sweden
Sahlgrenska University Hospital
Gothenburg, Sweden
Sahlgrenska University Hospital, Östra
Gothenburg, Sweden
Helsingborgs Hospital
Helsingborg, Sweden, 251 87
Karlstad Central Hospital
Karlstad, Sweden
Kungälv Hospital
Kungälv, Sweden
Linköping University Hospital
Linköping, Sweden
Skåne University Hospital
Lund, Sweden
Skåne University Hospital
Malmö, Sweden
Vrinnevi Hospital
Norrköping, Sweden
Norra Älvsborgs Läns Sjukhus
Trollhättan/Vänersborg, Sweden
Örebro University Hospital
Örebro, Sweden
Switzerland
University Hospital of Geneva
Geneva, Switzerland
Kantonspital St Gallen
St Gallen, Switzerland
United Kingdom
Royal Bournemouth Hospital
Bournemouth, United Kingdom
University Hospital of Wales
Cardiff, United Kingdom
Guy's and St Thomas NHS Trust
London, United Kingdom
St Georges' Hospital
London, United Kingdom
Royal Berkshire NHS Foundation Trust
Reading, United Kingdom
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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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
Study First Received: November 25, 2009
Last Updated: July 8, 2013
Health Authority: Sweden: Regional Ethical Review Board
Sweden: Region Skåne

Keywords provided by 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
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on November 27, 2014