Out of Hospital Cardiac ArrestTTH48NCT01689077
Time-differentiated Therapeutic Hypothermia
A study testing Therapeutic hypothermia in people with Out of Hospital Cardiac Arrest, run by University of Aarhus at 10 sites in 6 countries.
Trial summary
The purpose of this study is to determine if 48 hours of mild therapeutic hypothermia following out of hospital cardiac arrest gives a better cerebral outcome compared to 24 hours therapeutic hypothermia. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Out of Hospital Cardiac Arrest
- What is being tested?
- Therapeutic hypothermia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 355 participants
- Where
- 10 sitesin 6 countries
- Study dates
- Jan 2013to Jan 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Out of hospital cardiac arrest of suspected cardiac origin
- Return of spontaneous circulation (ROSC)
- Glasgow Coma Score < 8
- Estimated time interval from cardiac arrest to ROSC ≤ 60 min
Who cannot join
- OOH-CA of suspected origin other than cardiac
- In hospital Cardiac arrest
- Terminal disease
- Coagulation disorders
- Unwitnessed asystolia
- Time from cardiac arrest to start of hypothermia treatment > 240 min
Show all 13Show fewer
- GCS ≥ 8
- Pregnancy
- Persistent cardiogenic shock (Systolic blood pressure < 80 mmHg despite inotropic treatment and aortic balloon pump).
- CPC 3-4 before cardiac arrest
- Acute intra cerebral bleeding
- Acute stroke
- Acute coronary artery bypass grafting
Trial locations and contacts
10 sites in 6 countries.
10 sites in 6 countries
Denmark4 sites
Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aalborg
Aalborg, 9000
Department og Anesthesiologi and Intensive Care Medicine,
Aarhus, 8200
Department of Cardiology, Copenhagen University Hospital, Rigshospitalet
Copenhagen, 2100
Department of Anaesthesiology and Intensive Care Medicine, Odense University Hospital
Odense, 5000
Finland2 sites
Division of Anaesthesiology and Intensive Care Medicine, Department of Surgery, Helsinki University Central Hospital
Helsinki, 00029-HUS
Hospital District of Southwest Finland), Kiinamyllynkatu
Turku
Estonia1 site
Anaesthesiology Clinic, North Estonia Medical Centre
Tallinn, 13419
Germany1 site
Department of Internal Medicine, Nephrology and Intensive Care; Charité-Universitätsmedizin Berlin
Berlin
Norway1 site
Anesthesiology and Critical Care, Stavanger University Hospital
Stavanger, 4068
About this study
Official title: Time-differentiated Treatment With Mild Therapeutic Hypothermia Following Cardiac Arrest, a Multi Center Study.
The purpose of this study is to determine if 48 hours of mild therapeutic hypothermia following out of hospital cardiac arrest gives a better cerebral outcome compared to 24 hours therapeutic hypothermia.
Read the detailed description
Sudden out-of-hospital cardiac arrest (OOH-CA) remains a significant cause of death. However, in 2002 it was in two clinical trials demonstrated that mild therapeutic hypothermia in comatose OOH-CA victims yields a better cerebral outcome measured by Cerebral Performance Category Score (CPC) after 6 month. The optimal mild hypothermia treatment time is however not known. The two trials from 2002 apply the treatment for 12 and 24 hours respectively. In newborns with cerebral hypoxic damage the standard treatment time is 72 hours. It is therefore relevant to investigate the influence of the treatment time on the cerebral outcome in OOH-CA victims. In the present study cerebral outcome after mild therapeutic hypothermia (target temperature 33 degrees centigrade) in OOH-CA patients for 24 is compared to outcome after 48 hours of mild hypothermia. The main outcome parameter is mortality and CPC score measured 6 month after the treatment.
- Conditions
- Out of Hospital Cardiac Arrest
- Being tested
- Therapeutic hypothermia
- Medical subject headings
- Out-of-Hospital Cardiac Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Therapeutic hypothermiaOther
Mild therapeutic hypothermia with a target temperature of 33 degrees Centigrade for 24 or 48 hours
| Study group | Role | What they receive |
|---|---|---|
| 24 hours hypothermia | Active comparator | 24 hours hypothermia Receives: Other: Therapeutic hypothermia |
| 48 hours hypothermoa | Experimental | 48 hours hypothermia Receives: Other: Therapeutic hypothermia |
What is being measured
The primary outcome is the main question the study is designed to answer.
CPC
CPC = Cerebral Performance Category Score. The primary outcome of the study is analyzed as the proportion of patients with good neurological outcome in the two groups, (CPC 1-2) at 6 months after CA.
Measured: 6 month
Secondary outcomes (3)
Adverse events
Adverse events are registered during the treatment and until discharge from primary hospital unit
Measured: 10 days
CPC at discharge
CPC at discharge from primary hospital unit and after 28 days plus after 3 month
Measured: 3 month
Mortality
CPC 5 at 6 month
Measured: 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2012 (estimated)
- Study startJan 2013
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Out of Hospital Cardiac ArrestStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 355 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hans Kirkegaard, Professor, Principal investigator, Department of Anaesthesia and Intensive care medicine, Aarhus University Hosptal, Brendstrupgaardsvej 8200 Aarhus, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01689077
- Sponsor's protocol ID
- TTH48
- Acronym
- TTH48
- Status last verified
- Dec 2016
- First submitted
- 17 Sep 2012
- Last updated
- 18 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Evald L, Skrifvars MB, Virta JJ, Tiainen M, Laitio T, Leithner C, Soreide E, Hassager C, Rasmussen B, Grejs AM, Jeppesen AN, Kirkegaard H, Nielsen JF. Long-term functional outcome and quality of life 5-8 years after out of hospital cardiac arrest. Resuscitation. 2025 Oct;215:110672. doi: 10.1016/j.resuscitation.2025.110672. Epub 2025 Jun 9.
PubMed 40499675Larsen AI, Grejs AM, Vistisen ST, Strand K, Skadberg O, Jeppesen AN, Duez CHV, Kirkegaard H, Soreide E. Kinetics of 2 different high-sensitive troponins during targeted temperature management in out-of-hospital cardiac arrest patients with acute myocardial infarction: a post hoc sub-study of a randomised clinical trial. BMC Cardiovasc Disord. 2022 Jul 30;22(1):342. doi: 10.1186/s12872-022-02778-4.
PubMed 35907787Bach HM, Duez CHV, Jeppesen AN, Strand K, Soreide E, Kirkegaard H, Grejs AM. MR-proANP and NT-proBNP During Targeted Temperature Management Following Out-of-Hospital Cardiac Arrest: A Post hoc Analysis of the TTH48 Trial. Ther Hypothermia Temp Manag. 2022 Jun;12(2):82-89. doi: 10.1089/ther.2021.0012. Epub 2021 Aug 10.
PubMed 34375135Hastbacka J, Kirkegaard H, Soreide E, Taccone FS, Rasmussen BS, Storm C, Kjaergaard J, Laitio T, Duez CHV, Jeppesen AN, Grejs AM, Skrifvars MB. Severe or critical hypotension during post cardiac arrest care is associated with factors available on admission - a post hoc analysis of the TTH48 trial. J Crit Care. 2021 Feb;61:186-190. doi: 10.1016/j.jcrc.2020.10.026. Epub 2020 Nov 2.
PubMed 33181415Skrifvars MB, Soreide E, Sawyer KN, Taccone FS, Toome V, Storm C, Jeppesen A, Grejs A, Duez CHV, Tiainen M, Rasmussen BS, Laitio T, Hassager C, Kirkegaard H. Hypothermic to ischemic ratio and mortality in post-cardiac arrest patients. Acta Anaesthesiol Scand. 2020 Apr;64(4):546-555. doi: 10.1111/aas.13528. Epub 2019 Dec 26.
PubMed 31830304Evald L, Bronnick K, Duez CHV, Grejs AM, Jeppesen AN, Soreide E, Kirkegaard H, Nielsen JF. Prolonged targeted temperature management reduces memory retrieval deficits six months post-cardiac arrest: A randomised controlled trial. Resuscitation. 2019 Jan;134:1-9. doi: 10.1016/j.resuscitation.2018.12.002. Epub 2018 Dec 17.
PubMed 30572070Kirkegaard H, Soreide E, de Haas I, Pettila V, Taccone FS, Arus U, Storm C, Hassager C, Nielsen JF, Sorensen CA, Ilkjaer S, Jeppesen AN, Grejs AM, Duez CHV, Hjort J, Larsen AI, Toome V, Tiainen M, Hastbacka J, Laitio T, Skrifvars MB. Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2017 Jul 25;318(4):341-350. doi: 10.1001/jama.2017.8978.
PubMed 28742911Kirkegaard H, Pedersen AR, Pettila V, Hjort J, Rasmussen BS, de Haas I, Nielsen JF, Ilkjaer S, Kaltoft A, Jeppesen AN, Grejs AM, Duez CH, Larsen AI, Toome V, Arus U, Taccone FS, Storm C, Laitio T, Skrifvars MB, Soreide E. A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial. Scand J Trauma Resusc Emerg Med. 2016 Nov 28;24(1):138. doi: 10.1186/s13049-016-0334-0.
PubMed 27894327Kirkegaard H, Rasmussen BS, de Haas I, Nielsen JF, Ilkjaer S, Kaltoft A, Jeppesen AN, Grejs A, Duez CH, Larsen AI, Pettila V, Toome V, Arus U, Taccone FS, Storm C, Skrifvars MB, Soreide E. Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial. Trials. 2016 May 4;17(1):228. doi: 10.1186/s13063-016-1338-9.
PubMed 27142588
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Time-differentiated Treatment With Mild Therapeutic Hypothermia Following Cardiac Arrest, a Multi Center Study.
- ClinicalTrials.gov ID
- NCT01689077
- Acronym / sponsor ID
- TTH48 / TTH48
- Conditions
- Out of Hospital Cardiac Arrest
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 355 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 20 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if 48 hours of mild therapeutic hypothermia following out of hospital cardiac arrest gives a better cerebral outcome compared to 24 hours therapeutic hypothermia.
Detailed description
Sudden out-of-hospital cardiac arrest (OOH-CA) remains a significant cause of death. However, in 2002 it was in two clinical trials demonstrated that mild therapeutic hypothermia in comatose OOH-CA victims yields a better cerebral outcome measured by Cerebral Performance Category Score (CPC) after 6 month. The optimal mild hypothermia treatment time is however not known. The two trials from 2002 apply the treatment for 12 and 24 hours respectively. In newborns with cerebral hypoxic damage the standard treatment time is 72 hours. It is therefore relevant to investigate the influence of the treatment time on the cerebral outcome in OOH-CA victims. In the present study cerebral outcome after mild therapeutic hypothermia (target temperature 33 degrees centigrade) in OOH-CA patients for 24 is compared to outcome after 48 hours of mild hypothermia. The main outcome parameter is mortality and CPC score measured 6 month after the treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 24 hours hypothermia | Active comparator | Other: Therapeutic hypothermia24 hours hypothermia |
| 48 hours hypothermoa | Experimental | Other: Therapeutic hypothermia48 hours hypothermia |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Out of hospital cardiac arrest of suspected cardiac origin
- Return of spontaneous circulation (ROSC)
- Glasgow Coma Score < 8
- Estimated time interval from cardiac arrest to ROSC ≤ 60 min
Key exclusion criteria (13 listed)
- OOH-CA of suspected origin other than cardiac
- In hospital Cardiac arrest
- Terminal disease
- Coagulation disorders
- Unwitnessed asystolia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Therapeutic hypothermiaMild therapeutic hypothermia with a target temperature of 33 degrees Centigrade for 24 or 48 hours | Other | 24 hours hypothermia, 48 hours hypothermoa |
Primary outcome
CPC
Time frame: 6 month
CPC = Cerebral Performance Category Score. The primary outcome of the study is analyzed as the proportion of patients with good neurological outcome in the two groups, (CPC 1-2) at 6 months after CA.
3 secondary outcomes
Adverse events
Time frame: 10 days
CPC at discharge
Time frame: 3 month
Mortality
Time frame: 6 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2017.
- Derived from this study: PubMed 40499675Evald L, Skrifvars MB, Virta JJ, Tiainen M, Laitio T, Leithner C, Soreide E, Hassager C, Rasmussen B, Grejs AM, Jeppesen AN, Kirkegaard H, Nielsen JF. Long-term functional outcome and quality of life 5-8 years after out of hospital cardiac arrest. Resuscitation. 2025 Oct;215:110672. doi: 10.1016/j.resuscitation.2025.110672. Epub 2025 Jun 9.
- Derived from this study: PubMed 35907787Larsen AI, Grejs AM, Vistisen ST, Strand K, Skadberg O, Jeppesen AN, Duez CHV, Kirkegaard H, Soreide E. Kinetics of 2 different high-sensitive troponins during targeted temperature management in out-of-hospital cardiac arrest patients with acute myocardial infarction: a post hoc sub-study of a randomised clinical trial. BMC Cardiovasc Disord. 2022 Jul 30;22(1):342. doi: 10.1186/s12872-022-02778-4.
- Derived from this study: PubMed 34375135Bach HM, Duez CHV, Jeppesen AN, Strand K, Soreide E, Kirkegaard H, Grejs AM. MR-proANP and NT-proBNP During Targeted Temperature Management Following Out-of-Hospital Cardiac Arrest: A Post hoc Analysis of the TTH48 Trial. Ther Hypothermia Temp Manag. 2022 Jun;12(2):82-89. doi: 10.1089/ther.2021.0012. Epub 2021 Aug 10.
- Derived from this study: PubMed 33181415Hastbacka J, Kirkegaard H, Soreide E, Taccone FS, Rasmussen BS, Storm C, Kjaergaard J, Laitio T, Duez CHV, Jeppesen AN, Grejs AM, Skrifvars MB. Severe or critical hypotension during post cardiac arrest care is associated with factors available on admission - a post hoc analysis of the TTH48 trial. J Crit Care. 2021 Feb;61:186-190. doi: 10.1016/j.jcrc.2020.10.026. Epub 2020 Nov 2.
- Derived from this study: PubMed 31830304Skrifvars MB, Soreide E, Sawyer KN, Taccone FS, Toome V, Storm C, Jeppesen A, Grejs A, Duez CHV, Tiainen M, Rasmussen BS, Laitio T, Hassager C, Kirkegaard H. Hypothermic to ischemic ratio and mortality in post-cardiac arrest patients. Acta Anaesthesiol Scand. 2020 Apr;64(4):546-555. doi: 10.1111/aas.13528. Epub 2019 Dec 26.
- Derived from this study: PubMed 30572070Evald L, Bronnick K, Duez CHV, Grejs AM, Jeppesen AN, Soreide E, Kirkegaard H, Nielsen JF. Prolonged targeted temperature management reduces memory retrieval deficits six months post-cardiac arrest: A randomised controlled trial. Resuscitation. 2019 Jan;134:1-9. doi: 10.1016/j.resuscitation.2018.12.002. Epub 2018 Dec 17.
- Derived from this study: PubMed 28742911Kirkegaard H, Soreide E, de Haas I, Pettila V, Taccone FS, Arus U, Storm C, Hassager C, Nielsen JF, Sorensen CA, Ilkjaer S, Jeppesen AN, Grejs AM, Duez CHV, Hjort J, Larsen AI, Toome V, Tiainen M, Hastbacka J, Laitio T, Skrifvars MB. Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2017 Jul 25;318(4):341-350. doi: 10.1001/jama.2017.8978.
- Derived from this study: PubMed 27894327Kirkegaard H, Pedersen AR, Pettila V, Hjort J, Rasmussen BS, de Haas I, Nielsen JF, Ilkjaer S, Kaltoft A, Jeppesen AN, Grejs AM, Duez CH, Larsen AI, Toome V, Arus U, Taccone FS, Storm C, Laitio T, Skrifvars MB, Soreide E. A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial. Scand J Trauma Resusc Emerg Med. 2016 Nov 28;24(1):138. doi: 10.1186/s13049-016-0334-0.
- Derived from this study: PubMed 27142588Kirkegaard H, Rasmussen BS, de Haas I, Nielsen JF, Ilkjaer S, Kaltoft A, Jeppesen AN, Grejs A, Duez CH, Larsen AI, Pettila V, Toome V, Arus U, Taccone FS, Storm C, Skrifvars MB, Soreide E. Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial. Trials. 2016 May 4;17(1):228. doi: 10.1186/s13063-016-1338-9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hans Kirkegaard, Professor principal investigator
Department of Anaesthesia and Intensive care medicine, Aarhus University Hosptal, Brendstrupgaardsvej 8200 Aarhus, Denmark
10 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Therapeutic hypothermia in people with Out of Hospital Cardiac Arrest, run by University of Aarhus at 10 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Denmark, Finland, Belgium, Estonia, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CPC (time frame: 6 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01689077, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2017.