Time-differentiated Therapeutic Hypothermia

NCT ID: NCT01689077

Last Updated: 2017-01-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

355 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2017-01-31

Brief Summary

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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

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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

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Out of Hospital Cardiac Arrest

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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24 hours hypothermia

24 hours hypothermia

Group Type ACTIVE_COMPARATOR

Therapeutic hypothermia

Intervention Type OTHER

Mild therapeutic hypothermia with a target temperature of 33 degrees Centigrade for 24 or 48 hours

48 hours hypothermoa

48 hours hypothermia

Group Type EXPERIMENTAL

Therapeutic hypothermia

Intervention Type OTHER

Mild therapeutic hypothermia with a target temperature of 33 degrees Centigrade for 24 or 48 hours

Interventions

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Therapeutic hypothermia

Mild therapeutic hypothermia with a target temperature of 33 degrees Centigrade for 24 or 48 hours

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Out of hospital cardiac arrest of suspected cardiac origin
2. Return of spontaneous circulation (ROSC)
3. Glasgow Coma Score \< 8
4. Estimated time interval from cardiac arrest to ROSC ≤ 60 min

Exclusion Criteria

1. OOH-CA of suspected origin other than cardiac
2. In hospital Cardiac arrest
3. Terminal disease
4. Coagulation disorders
5. Unwitnessed asystolia
6. Time from cardiac arrest to start of hypothermia treatment \> 240 min
7. GCS ≥ 8
8. Pregnancy
9. Persistent cardiogenic shock (Systolic blood pressure \< 80 mmHg despite inotropic treatment and aortic balloon pump).
10. CPC 3-4 before cardiac arrest
11. Acute intra cerebral bleeding
12. Acute stroke
13. Acute coronary artery bypass grafting
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Aarhus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hans Kirkegaard, Professor

Role: PRINCIPAL_INVESTIGATOR

Department of Anaesthesia and Intensive care medicine, Aarhus University Hosptal, Brendstrupgaardsvej 8200 Aarhus, Denmark

Locations

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Department of Intensive Care, Erasme Hospital

Brussels, , Belgium

Site Status

Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aalborg

Aalborg, , Denmark

Site Status

Department og Anesthesiologi and Intensive Care Medicine,

Aarhus, , Denmark

Site Status

Department of Cardiology, Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status

Department of Anaesthesiology and Intensive Care Medicine, Odense University Hospital

Odense, , Denmark

Site Status

Anaesthesiology Clinic, North Estonia Medical Centre

Tallinn, , Estonia

Site Status

Division of Anaesthesiology and Intensive Care Medicine, Department of Surgery, Helsinki University Central Hospital

Helsinki, , Finland

Site Status

Hospital District of Southwest Finland), Kiinamyllynkatu

Turku, , Finland

Site Status

Department of Internal Medicine, Nephrology and Intensive Care; Charité-Universitätsmedizin Berlin

Berlin, , Germany

Site Status

Anesthesiology and Critical Care, Stavanger University Hospital

Stavanger, , Norway

Site Status

Countries

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Belgium Denmark Estonia Finland Germany Norway

References

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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.

Reference Type DERIVED
PMID: 40499675 (View on PubMed)

Larsen 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.

Reference Type DERIVED
PMID: 35907787 (View on PubMed)

Bach 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.

Reference Type DERIVED
PMID: 34375135 (View on PubMed)

Hastbacka 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.

Reference Type DERIVED
PMID: 33181415 (View on PubMed)

Skrifvars 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.

Reference Type DERIVED
PMID: 31830304 (View on PubMed)

Evald 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.

Reference Type DERIVED
PMID: 30572070 (View on PubMed)

Kirkegaard 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.

Reference Type DERIVED
PMID: 28742911 (View on PubMed)

Kirkegaard 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.

Reference Type DERIVED
PMID: 27894327 (View on PubMed)

Kirkegaard 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.

Reference Type DERIVED
PMID: 27142588 (View on PubMed)

Other Identifiers

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TTH48

Identifier Type: -

Identifier Source: org_study_id

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