Clinical trial NCT01689077: Time-differentiated Therapeutic Hypothermia
Official title: Time-differentiated Treatment With Mild Therapeutic Hypothermia Following Cardiac Arrest, a Multi Center Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Out of Hospital Cardiac Arrest
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2012-09-20
Enrollment: 355
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: CPC
timeFrame: 6 month
Secondary outcomes:
measure: Adverse events
timeFrame: 10 days
measure: CPC at discharge
timeFrame: 3 month
measure: Mortality
timeFrame: 6 month
Other outcomes:
measure: GCS
timeFrame: 28 days
measure: GCS progression
timeFrame: 25 weeks
Locations:
city: Brussels
country: Belgium
facility: Department of Intensive Care, Erasme Hospital
city: Aalborg
country: Denmark
facility: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aalborg
city: Aarhus
country: Denmark
facility: Department og Anesthesiologi and Intensive Care Medicine,
city: Copenhagen
country: Denmark
facility: Department of Cardiology, Copenhagen University Hospital, Rigshospitalet
city: Odense
country: Denmark
facility: Department of Anaesthesiology and Intensive Care Medicine, Odense University Hospital
city: Tallinn
country: Estonia
facility: Anaesthesiology Clinic, North Estonia Medical Centre
city: Helsinki
country: Finland
facility: Division of Anaesthesiology and Intensive Care Medicine, Department of Surgery, Helsinki University Central Hospital
city: Turku
country: Finland
facility: Hospital District of Southwest Finland), Kiinamyllynkatu
city: Berlin
country: Germany
facility: Department of Internal Medicine, Nephrology and Intensive Care; Charité-Universitätsmedizin Berlin
city: Stavanger
country: Norway
facility: Anesthesiology and Critical Care, Stavanger University Hospital
Study officials:
affiliation: Department of Anaesthesia and Intensive care medicine, Aarhus University Hosptal, Brendstrupgaardsvej 8200 Aarhus, Denmark
name: Hans Kirkegaard, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.