Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000477921
Ethics application status
Approved
Date submitted
14/04/2011
Date registered
9/05/2011
Date last updated
27/03/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Target Temperature Management after cardiac arrest Trial
Scientific title
A multi-centre randomised, parallel group, assessor-blinded clinical trial to compare all-cause mortality between a target temperature management of 33 degrees Celsius versus a target temperature management of 36 degrees Celsius after out-of-hospital cardiac arrest
Secondary ID [1] 259962 0
ClinicalTrials.gov: NCT01020916
Universal Trial Number (UTN)
Trial acronym
TTM-Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Out-of-hospital cardiac arrest 265594 0
Condition category
Condition code
Cardiovascular 265743 265743 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Target temperature of 33 degrees Celsius.

Patients will be managed with 24 hours of temperature control at a target temperature of 33 degrees Celsius. Temperature management will be delivered with commercially available equipment at the discretion of each trial site. The type of equipment used for a specific patient will be registered prior to randomisation. When applicable, to facilitate cooling and to stabilise circulation, patients will be treated with crystalloid infusion (4 degrees Celsius or room temperature according to treatment arm) at the discretion of the treating physician.

Intervention period begins when the first temperature measurement to achieve the assigned target temperature, is taken. Patients are mechanically ventilated and sedated as per standard practice. Patients are treated for 24 hours with temperature management devices to achieve a target temperature of 33 degrees Celsius. Patients are then rewarmed to a body temperature of 37 degrees Celsius within the following 8 hours, with a rewarming rate of 0.5 degrees per hour.

Sedation will be ceased or tapered once temperature reaches 37 degrees Celsius. Normothermia of 37 degrees +/- 0.5 degrees Celsius is maintained for 36 hours.
Intervention code [1] 264381 0
Treatment: Other
Comparator / control treatment
Target temperature of 36 degrees Celsius
Control group
Active

Outcomes
Primary outcome [1] 266498 0
All-cause mortality
Timepoint [1] 266498 0
180 days
Secondary outcome [1] 273896 0
Composite outcome of all-cause mortality and poor neurological function (CPC 3 and 4)
Timepoint [1] 273896 0
Hospital discharge and at 180 days
Secondary outcome [2] 273897 0
All-cause mortality
Timepoint [2] 273897 0
Hospital discharge
Secondary outcome [3] 273898 0
Cerebral Performance Category (CPC)
Timepoint [3] 273898 0
Hospital discharge and at 180 days
Secondary outcome [4] 273899 0
Neurological function will be assessed by an assessor blinded to the intervention allocation.

Quality of life assessment will also be evaluated by the blinded assessor, using Mini Mental Test, IQCODE, Modified Rankin Scale and Short Form 36.

These follow up assessments attended by the blinded assessor will be performed via a telephone call to the patient and/or the patient's substitute decision maker.
Timepoint [4] 273899 0
180 days
Secondary outcome [5] 273900 0
Best neurological outcome according to the CPC-scale
Timepoint [5] 273900 0
Baseline until 180 days
Secondary outcome [6] 273901 0
Safety measures: Bleeding, pneumonia, sepsis, electrolyte disorders, hyperglycaemia, hypoglycaemia, cardiac arrhythmia and the need for renal replacement therapy.

All adverse events will be recorded daily for the first 7 days, whilst the patient is in the ICU. Any adverse event occurring during the trial will be treated according to standard practice and the patient will be followed until the event has disappeared or until the condition has stabilised.

All adverse events (AE, SAE, SUSAR) are reviewed by the Data Safety Monitoring Board.
Timepoint [6] 273901 0
Baseline until 7 days (whilst patient in ICU)

Eligibility
Key inclusion criteria
1. Age greater than or equal to 18 years
2. OHCA of presumed cardiac cause
3. Sustained ROSC*
4. Unconsciousness (GCS <8) (patients not able to obey verbal commands) after sustained ROSC

* Sustained ROSC: Sustained ROSC is when chest compressions have been not required for 20 consecutive minutes and signs of circulation persist
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Conscious patients (obeying verbal commands)
2. Pregnancy
3. In-hospital cardiac arrest (IHCA)
4. 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)
5. Known bleeding diathesis (medically induced coagulopathy e.g. warfarin, clopidogrel, does not exclude the patient)
6. Suspected or confirmed acute intracranial bleeding
7. Suspected or confirmed acute stroke
8. Unwitnessed asystole
9. A limitation of therapy order has been documented restricting implementation of the study protocol or the treating clinician deems aggressive care unsuitable
10. Known underlying disease making 180 day survival unlikely
11. Known pre-arrest CPC 3 or 4
12. >4 hours (240 minutes) from ROSC to screening
13. Systolic blood pressure <80 mmHg in spite of fluid loading/vasopressor and/or inotropic medication/intra aortic balloon pump#
14. Temperature on admission <30 degrees Celsius

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)
Central randomisation via website.
Allocation is not concealed from treating clinicians.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be achieved by dynamic blocks via a password-protected encrypted website. Randomisation will be stratified according to participating trial site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2010
Actual
1/01/2011
Date of last participant enrolment
Anticipated
Actual
11/01/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
850
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 3926 0
2170
Recruitment postcode(s) [2] 3927 0
2560
Recruitment postcode(s) [3] 3928 0
2622
Recruitment postcode(s) [4] 3998 0
2065
Recruitment outside Australia
Country [1] 3348 0
Sweden
State/province [1] 3348 0
Helsingborg
Country [2] 3349 0
Sweden
State/province [2] 3349 0
Lund
Country [3] 3350 0
Sweden
State/province [3] 3350 0
Malmo
Country [4] 3351 0
Sweden
State/province [4] 3351 0
karlstad
Country [5] 3352 0
Sweden
State/province [5] 3352 0
Linkoping
Country [6] 3353 0
Sweden
State/province [6] 3353 0
Molndal
Country [7] 3354 0
Sweden
State/province [7] 3354 0
Norrkoping
Country [8] 3355 0
Sweden
State/province [8] 3355 0
Gothenburg
Country [9] 3356 0
Sweden
State/province [9] 3356 0
Orebro
Country [10] 3357 0
Czech Republic
State/province [10] 3357 0
Prague
Country [11] 3358 0
Denmark
State/province [11] 3358 0
Copenhagen
Country [12] 3359 0
Denmark
State/province [12] 3359 0
Gentofte
Country [13] 3360 0
Germany
State/province [13] 3360 0
Berlin
Country [14] 3361 0
Germany
State/province [14] 3361 0
Bonn
Country [15] 3362 0
Hungary
State/province [15] 3362 0
Budapest
Country [16] 3363 0
Iceland
State/province [16] 3363 0
Reykjavik
Country [17] 3364 0
Italy
State/province [17] 3364 0
Trento
Country [18] 3365 0
Italy
State/province [18] 3365 0
Trieste
Country [19] 3366 0
Italy
State/province [19] 3366 0
Pordenone
Country [20] 3367 0
Italy
State/province [20] 3367 0
Siena
Country [21] 3368 0
Luxembourg
State/province [21] 3368 0
Luxembourg
Country [22] 3369 0
Netherlands
State/province [22] 3369 0
Amsterdam
Country [23] 3370 0
Netherlands
State/province [23] 3370 0
leeuwarden
Country [24] 3371 0
Norway
State/province [24] 3371 0
Oslo
Country [25] 3372 0
Norway
State/province [25] 3372 0
Bergen
Country [26] 3373 0
Switzerland
State/province [26] 3373 0
Geneva
Country [27] 3374 0
Switzerland
State/province [27] 3374 0
lausanne
Country [28] 3375 0
United Kingdom
State/province [28] 3375 0
Cardiff
Country [29] 3376 0
United Kingdom
State/province [29] 3376 0
Reading
Country [30] 3377 0
United Kingdom
State/province [30] 3377 0
Dorset

Funding & Sponsors
Funding source category [1] 264854 0
Charities/Societies/Foundations
Name [1] 264854 0
Swedish Heart and Lung Foundation
Country [1] 264854 0
Sweden
Funding source category [2] 264897 0
Charities/Societies/Foundations
Name [2] 264897 0
AFA-Foundation
Country [2] 264897 0
Sweden
Funding source category [3] 264898 0
Charities/Societies/Foundations
Name [3] 264898 0
Stig and Ragna Gorthon Foundation
Country [3] 264898 0
Sweden
Funding source category [4] 264899 0
Charities/Societies/Foundations
Name [4] 264899 0
Gyllenstierna Krapperup Foundation
Country [4] 264899 0
Sweden
Funding source category [5] 264901 0
Charities/Societies/Foundations
Name [5] 264901 0
ACTA Foundation within the Scandinavian Society of Anaesthesiology and Intensive Care
Country [5] 264901 0
Denmark
Funding source category [6] 265008 0
Charities/Societies/Foundations
Name [6] 265008 0
Torsten Birger Segerfalk Foundation
Country [6] 265008 0
Sweden
Funding source category [7] 265009 0
Government body
Name [7] 265009 0
Region Skane
Country [7] 265009 0
Sweden
Funding source category [8] 265010 0
Government body
Name [8] 265010 0
Governmental funding for clinical research
Country [8] 265010 0
Sweden
Primary sponsor type
Hospital
Name
Helsingborg Hospital
Address
S Vallgatan 5
S-251 87 Helsingborg
Lund University
Lund
Country
Sweden
Secondary sponsor category [1] 263998 0
Other Collaborative groups
Name [1] 263998 0
Scandinavian Critical Care Trials Group
Address [1] 263998 0
Hjejle, Gersted and Mogensen Law Firm
24, Amagertorv
DK 1160, Copenhagen
Country [1] 263998 0
Denmark
Secondary sponsor category [2] 263999 0
Other Collaborative groups
Name [2] 263999 0
Copenhagen Trial Unit, Centre for Clinical Intervention Research
Address [2] 263999 0
Rigshospitalet
Dept. 33.44
DK-2100
Copenhagen
Country [2] 263999 0
Denmark
Other collaborator category [1] 251956 0
Other
Name [1] 251956 0
The George Institute for Global Health
Address [1] 251956 0
Level 7
341 George Street
Sydney NSW 2000
Country [1] 251956 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 267000 0
Research Ethics Committee for Wales
Ethics committee address [1] 267000 0
Ethics committee country [1] 267000 0
United Kingdom
Date submitted for ethics approval [1] 267000 0
22/11/2010
Approval date [1] 267000 0
21/12/2010
Ethics approval number [1] 267000 0
10/MRE09/41
Ethics committee name [2] 267005 0
National Ethics Research Committee
Ethics committee address [2] 267005 0
Ethics committee country [2] 267005 0
Luxembourg
Date submitted for ethics approval [2] 267005 0
22/06/2010
Approval date [2] 267005 0
12/07/2010
Ethics approval number [2] 267005 0
201007/05
Ethics committee name [3] 267009 0
Medical Ethics Research Committee
Ethics committee address [3] 267009 0
Ethics committee country [3] 267009 0
Netherlands
Date submitted for ethics approval [3] 267009 0
Approval date [3] 267009 0
22/11/2010
Ethics approval number [3] 267009 0
1/10/0107
Ethics committee name [4] 267010 0
Regional Ethics Research Committee
Ethics committee address [4] 267010 0
Ethics committee country [4] 267010 0
Sweden
Date submitted for ethics approval [4] 267010 0
Approval date [4] 267010 0
11/11/2010
Ethics approval number [4] 267010 0
2010/615
Ethics committee name [5] 267011 0
Science Committee of Capital Region
Ethics committee address [5] 267011 0
Ethics committee country [5] 267011 0
Denmark
Date submitted for ethics approval [5] 267011 0
21/09/2010
Approval date [5] 267011 0
27/09/2010
Ethics approval number [5] 267011 0
H-1-2010-059
Ethics committee name [6] 267012 0
Regional Research Ethics Committee
Ethics committee address [6] 267012 0
Ethics committee country [6] 267012 0
Norway
Date submitted for ethics approval [6] 267012 0
25/02/2010
Approval date [6] 267012 0
15/06/2010
Ethics approval number [6] 267012 0
2010/384
Ethics committee name [7] 267013 0
Independent Ethics Committee of Azienda Hospital
Ethics committee address [7] 267013 0
Ethics committee country [7] 267013 0
Italy
Date submitted for ethics approval [7] 267013 0
22/11/2010
Approval date [7] 267013 0
02/03/2011
Ethics approval number [7] 267013 0
9
Ethics committee name [8] 267014 0
Ethics Committee for Clinical Trials
Ethics committee address [8] 267014 0
Ethics committee country [8] 267014 0
Italy
Date submitted for ethics approval [8] 267014 0
Approval date [8] 267014 0
10/02/2011
Ethics approval number [8] 267014 0
19292694
Ethics committee name [9] 267015 0
Ethics Committee of the General University Hospital, Prague
Ethics committee address [9] 267015 0
Ethics committee country [9] 267015 0
Czech Republic
Date submitted for ethics approval [9] 267015 0
07/02/2011
Approval date [9] 267015 0
17/02/2011
Ethics approval number [9] 267015 0
193/11 S
Ethics committee name [10] 267016 0
Research Ethics Committee
Ethics committee address [10] 267016 0
Ethics committee country [10] 267016 0
Switzerland
Date submitted for ethics approval [10] 267016 0
14/02/2011
Approval date [10] 267016 0
01/03/2011
Ethics approval number [10] 267016 0
10-254 (NAC 10-088)

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 9 9 0 0
/AnzctrAttachments/336785-TTM Publication_Rationale & Design_Apr 2012.pdf
Attachments [2] 10 10 0 0
/AnzctrAttachments/336785-TTM_Results Publication_NEJMoa1310519.pdf
Attachments [3] 11 11 0 0
/AnzctrAttachments/336785-TTM_Results Publication_NEJMoa1310519_Appendices.pdf

Contacts
Principal investigator
Name 32463 0
A/Prof Anders Aneman
Address 32463 0
Intensive Care Unit
Liverpool Hospital
Locked Bag 7103
Liverpool BC NSW 1871
Country 32463 0
Australia
Phone 32463 0
+61 2 8738 3400
Fax 32463 0
Email 32463 0
Anders.Aneman@sswahs.nsw.gov.au
Contact person for public queries
Name 15710 0
A/Prof Anders Aneman
Address 15710 0
Intensive Care Unit
Liverpool Hospital
Locked Bag 7103
Liverpool BC NSW 1871
Country 15710 0
Australia
Phone 15710 0
+61 2 8738 3400
Fax 15710 0
+61 2 8738 3551
Email 15710 0
Anders.Aneman@sswahs.nsw.gov.au
Contact person for scientific queries
Name 6638 0
Dr Niklas Nielsen
Address 6638 0
Department of Anaesthesiology and Intensive Care
Helsingborg Hospital
S Vallgatan 5
S-251 87 Helsingborg
Lund University
Lund
Country 6638 0
Sweden
Phone 6638 0
+ 46 4 2406 1000
Fax 6638 0
Email 6638 0
niklas.nielsen@telia.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No additional documents have been identified.