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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02908308




Registration number
NCT02908308
Ethics application status
Date submitted
16/09/2016
Date registered
20/09/2016
Date last updated
22/01/2020

Titles & IDs
Public title
Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest
Scientific title
Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) - A Randomised Clinical Trial
Secondary ID [1] 0 0
TTM-2
Universal Trial Number (UTN)
Trial acronym
TTM-2
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 - Targeted temperature management to 33°C
Treatment: Surgery - Standard care with early treatment of fever

Active Comparator: Normothermia - Standard care with early treatment of fever. Active temperature control with a device will be used if the patient develops a temperature greater than or equal 37.8°C.

Experimental: Hypothermia - Targeted temperature management to 33°C for up to 28h.


Treatment: Surgery: Targeted temperature management to 33°C
Rapid cooling to below 33°C, followed by temperature control at 33°C for up to 28h.

Treatment: Surgery: Standard care with early treatment of fever
Normothermia and standard care - use of a device for temperature control if temperature is greater than or equal to 37.8°C

Intervention code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mortality - Landmark mortality at 180 days
Timepoint [1] 0 0
180 days
Secondary outcome [1] 0 0
Poor functional outcome - Assessed using the modified Rankin Scale (mRS), with a score of 4-6 being a poor outcome.
Timepoint [1] 0 0
180 days
Secondary outcome [2] 0 0
Days alive outside hospital - Number of days alive within 180 days from initial hospital discharge.
Timepoint [2] 0 0
180 days.
Secondary outcome [3] 0 0
Quality of Life - Health-related Quality of Life - EQ-5D (VAS scale)
Timepoint [3] 0 0
180 days
Secondary outcome [4] 0 0
Quality of Life - Health-related Quality of Life - EQ-5D (Index value)
Timepoint [4] 0 0
180 days
Secondary outcome [5] 0 0
Survival until end of the trial - Mortality.
Timepoint [5] 0 0
180 days after randmomization of the last patient

Eligibility
Key inclusion criteria
- Out-of-hospital cardiac arrest

- Presumed cardiac cause of cardiac arrest

- Unconscious with a FOUR-score <M4 (not obeying verbal commands)

- Stable return of spontaneous circulation (20 min)

- Eligible for intensive care treatment without restrictions

- Inclusion within 180 minutes of ROSC
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Unwitnessed cardiac arrest with an initial rhythm of asystole

- Temperature on admission <30°C.

- On ECMO prior to ROSC

- Obvious or suspected pregnancy

- Intracranial bleeding

- On ECMO prior to ROSC

- Severe chronic obstructive pulmonary disorder (COPD) with long-term home oxygen
therapy

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Sydney
Recruitment hospital [3] 0 0
Liverpool Hospital - Sydney
Recruitment hospital [4] 0 0
St Vincent's Hospital - Sydney
Recruitment hospital [5] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [6] 0 0
Northern Hospital - Epping
Recruitment hospital [7] 0 0
The Alfred - Melbourne
Recruitment hospital [8] 0 0
Austin Hospital - Melbourne
Recruitment hospital [9] 0 0
Nepean Hospital - Sydney
Recruitment hospital [10] 0 0
Royal North Shore Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Newcastle
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
- Epping
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
Austria
State/province [3] 0 0
Innsbruck
Country [4] 0 0
Belgium
State/province [4] 0 0
Brussels
Country [5] 0 0
Belgium
State/province [5] 0 0
Genk
Country [6] 0 0
Czechia
State/province [6] 0 0
Hradec Králové
Country [7] 0 0
Czechia
State/province [7] 0 0
Liberec
Country [8] 0 0
Czechia
State/province [8] 0 0
Prague
Country [9] 0 0
Denmark
State/province [9] 0 0
Aarhus
Country [10] 0 0
France
State/province [10] 0 0
Limoges
Country [11] 0 0
France
State/province [11] 0 0
Nantes
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Versailles
Country [14] 0 0
Germany
State/province [14] 0 0
Berlin
Country [15] 0 0
Italy
State/province [15] 0 0
Genova
Country [16] 0 0
Italy
State/province [16] 0 0
Modena
Country [17] 0 0
New Zealand
State/province [17] 0 0
Christchurch
Country [18] 0 0
New Zealand
State/province [18] 0 0
Wellington
Country [19] 0 0
Norway
State/province [19] 0 0
Arendal
Country [20] 0 0
Norway
State/province [20] 0 0
Bergen
Country [21] 0 0
Norway
State/province [21] 0 0
Oslo
Country [22] 0 0
Norway
State/province [22] 0 0
Trondheim
Country [23] 0 0
Sweden
State/province [23] 0 0
Halland
Country [24] 0 0
Sweden
State/province [24] 0 0
Skåne
Country [25] 0 0
Sweden
State/province [25] 0 0
Gothenburg
Country [26] 0 0
Sweden
State/province [26] 0 0
Helsingborg
Country [27] 0 0
Sweden
State/province [27] 0 0
Karlstad
Country [28] 0 0
Sweden
State/province [28] 0 0
Linköping
Country [29] 0 0
Sweden
State/province [29] 0 0
Skövde
Country [30] 0 0
Sweden
State/province [30] 0 0
Stockholm
Country [31] 0 0
Sweden
State/province [31] 0 0
Trollhättan
Country [32] 0 0
Sweden
State/province [32] 0 0
Uppsala
Country [33] 0 0
Sweden
State/province [33] 0 0
Örebro
Country [34] 0 0
Switzerland
State/province [34] 0 0
Bern
Country [35] 0 0
Switzerland
State/province [35] 0 0
Lausanne
Country [36] 0 0
Switzerland
State/province [36] 0 0
Lugano
Country [37] 0 0
Switzerland
State/province [37] 0 0
Saint Gallen
Country [38] 0 0
Switzerland
State/province [38] 0 0
Zürich
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Basildon
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Belfast
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Birmingham
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Bournemouth
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Bristol
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Cardiff
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Manchester
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Portsmouth
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Reading

Funding & Sponsors
Primary sponsor type
Other
Name
Helsingborgs Hospital
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Lund University
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Region Skåne - Skånevård SUND
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Copenhagen Trial Unit, Center for Clinical Intervention Research
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Clinical Trials Sweden, Forum South
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Integrated Biobank of Luxembourg
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
ILCOR guidelines recommend Target Temperature Management (TTM) to between 32°C and 36°C after
out-of-hospital cardiac arrest, based on low quality evidence. In a previous trial, TTM at
33°C did not confer a survival benefit or improved neurological function, compared to TTM at
36°C. A lower target temperature might be beneficial compared with normothermia and early
treatment of fever. Therefore the primary purpose of the TTM2-trial will be to study any
differences in mortality, neurological function and quality of life between a target
temperature of 33°C and standard care avoiding fever.
Trial website
https://clinicaltrials.gov/show/NCT02908308
Trial related presentations / publications
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.
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
Other publications