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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01020916




Registration number
NCT01020916
Ethics application status
Date submitted
25/11/2009
Date registered
26/11/2009
Date last updated
10/07/2013

Titles & IDs
Public title
Target Temperature Management After Cardiac Arrest
Scientific title
Target Temperature Management 33°C Versus 36°C After Out-of-hospital Cardiac Arrest, a Randomised, Parallel Groups, Assessor Blinded Clinical Trial
Secondary ID [1] 0 0
TTM-1
Universal Trial Number (UTN)
Trial acronym
TTM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Out-of-hospital Cardiac Arrest 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Target temperature 36°C
Treatment: Surgery - Target Temperature 33°C

Experimental: Target Temperature 33°C -

Active Comparator: Target Temperature 36°C -


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

Treatment: Surgery: Target Temperature 33°C
In hospital target temperature management to achieve a core body temperature of 33°C for 24 hours
Intervention code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
All-cause mortality
Timepoint [1] 0 0
Maximum follow-up with a minimum of 180 days
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
180 days
Secondary outcome [2] 0 0
Bleeding
Timepoint [2] 0 0
During day 1-7 of intensive care treatment
Secondary outcome [3] 0 0
Neurological function
Timepoint [3] 0 0
180 days
Secondary outcome [4] 0 0
Pneumonia
Timepoint [4] 0 0
During day 1-7 of intensive care treatment
Secondary outcome [5] 0 0
Electrolyte disorders
Timepoint [5] 0 0
During day 1-7 of intensive care treatment
Secondary outcome [6] 0 0
Hyperglycaemia > 10 mmol/l
Timepoint [6] 0 0
During day 1-7 of intensive care treatment
Secondary outcome [7] 0 0
Hypoglycemia < 3mmol/l
Timepoint [7] 0 0
During day 1-7 of intensive care treatment
Secondary outcome [8] 0 0
Cardiac arrhythmia
Timepoint [8] 0 0
During day 1-7 of intensive care treatment
Secondary outcome [9] 0 0
The need for renal replacement therapy
Timepoint [9] 0 0
During day 1-7 of intensive care treatment
Secondary outcome [10] 0 0
Landmark all-cause mortality
Timepoint [10] 0 0
180 days
Secondary outcome [11] 0 0
Cerebral Performance Category (CPC)
Timepoint [11] 0 0
180 days
Secondary outcome [12] 0 0
Modified Rankin Scale (mRS)
Timepoint [12] 0 0
180 days

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2013
Sample size
Target
950
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Liverpool Hospital - Sydney
Recruitment hospital [2] 0 0
North Shore Hospital - Sydney
Recruitment hospital [3] 0 0
St George Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
Czech Republic
State/province [1] 0 0
Prague
Country [2] 0 0
Denmark
State/province [2] 0 0
Copenhagen
Country [3] 0 0
Italy
State/province [3] 0 0
Genova
Country [4] 0 0
Italy
State/province [4] 0 0
Pordenone
Country [5] 0 0
Italy
State/province [5] 0 0
Trieste
Country [6] 0 0
Luxembourg
State/province [6] 0 0
Luxembourg
Country [7] 0 0
Netherlands
State/province [7] 0 0
Amsterdam
Country [8] 0 0
Netherlands
State/province [8] 0 0
Arnhem
Country [9] 0 0
Netherlands
State/province [9] 0 0
Leeuwarden
Country [10] 0 0
Norway
State/province [10] 0 0
Bergen
Country [11] 0 0
Norway
State/province [11] 0 0
Oslo
Country [12] 0 0
Sweden
State/province [12] 0 0
Gothenburg
Country [13] 0 0
Sweden
State/province [13] 0 0
Helsingborg
Country [14] 0 0
Sweden
State/province [14] 0 0
Karlstad
Country [15] 0 0
Sweden
State/province [15] 0 0
Kungälv
Country [16] 0 0
Sweden
State/province [16] 0 0
Linköping
Country [17] 0 0
Sweden
State/province [17] 0 0
Lund
Country [18] 0 0
Sweden
State/province [18] 0 0
Malmö
Country [19] 0 0
Sweden
State/province [19] 0 0
Norrköping
Country [20] 0 0
Sweden
State/province [20] 0 0
Trollhättan/Vänersborg
Country [21] 0 0
Sweden
State/province [21] 0 0
Örebro
Country [22] 0 0
Switzerland
State/province [22] 0 0
Geneva
Country [23] 0 0
Switzerland
State/province [23] 0 0
St Gallen
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Bournemouth
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Cardiff
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Reading

Funding & Sponsors
Primary sponsor type
Other
Name
Niklas Nielsen
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Scandinavian Critical Care Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Copenhagen Trial Unit, Center for Clinical Intervention Research
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Lund University
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
The George Institute for Global Health, Australia
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01020916
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Niklas Nielsen, MD, PhD
Address 0 0
Helsingborgs lasarett, Region Skåne, Sweden
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01020916