Hypothermia and Hemostasis After Cardiac Arrest

The Effect of Therapeutic Hypothermia After Cardiac Arrest on the Haemostasis.

This is a sub-study to the Time-differentiated Therapeutic Hypothermia (TTH48, ClinicalTrials.gov Identifier: NCT01689077). TTH48 compares 24 with 48 hours of therapeutic hypothermia at a target temperature of 32-34°C in survivors of out-of-hospital cardiac arrest.

The overall aim of this sub-study is to examine the hemostasis in patients resuscitated after cardiac arrest and treated with 24 and 48 hours of therapeutic hypothermia

Our specific aims are:

• To investigate the whole blood coagulation using the rotational thromboelastometry.
• To investigate the function of platelets

Study Overview

• Status: Unknown
• Conditions: Heart Arrest; Hypothermia; Hemostasis; Coagulants
• Intervention / Treatment: Other: Therapeutic hypothermia

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N
    • Aarhus, Aarhus N, Denmark, 8200
      • Dept of Anesthesiology and Intensive Care and Dept of Clinical Biochemistry, Aarhus University Hospital, Skejby

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Out of hospital cardiac arrest of presumed cardiac cause
• Return of spontaneous circulation (ROSC)
• Glasgow Coma Score < 8
• Age > 18 years and < 80 years

Exclusion Criteria:

• > 60 minutes from the circulatory collapse to ROSC
• Time interval > 4 hours from cardiac arrest to initiation of therapeutic hypothermia
• Terminal illness
• Coagulation disorder
• Unwitnessed asystolia
• Cerebral performance category 3-4 before the cardiac arrest
• Severe persistent cardiogenic shock
• Pregnancy
• Persistent cardiogenic shock (systolic blood pressure < 80 despite inotropic treatment)
• New apoplexy or intracerebral hemorrhage
• Lack of consent from the relatives
• Lack of consent from the GP
• Lack of consent from the patient if he/she wakes up and is relevant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 24 hours hypothermia; Therapeutic hypothermia for 24 hours after reaching target temperature	Other: Therapeutic hypothermia; Therapeutic hypothermia with a target temperature between 32-34°C.
Experimental: 48 hours hypothermia; Therapeutic hypothermia for 48 hours after reaching target temperature	Other: Therapeutic hypothermia; Therapeutic hypothermia with a target temperature between 32-34°C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clotting time in seconds, EXTEM	Measured by thomboelastometry on the ROTEM®	After 46 hours
Area under the curve, COL-test	Platelet function will be measured using Multiplate®	After 46 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clotting time in seconds, EXTEM	Measured by thomboelastometry on the ROTEM®.	After 22 hours and 70 hours
Clotting time in seconds, -INTEM, FIBTEM and HEPTEM	Measured by thomboelastometry on the ROTEM®.	After 22 hours, 46 hours and 70 hours
Clot formation time in seconds, -EXTEM, INTEM, FIBTEM and HEPTEM	Measured by thomboelastometry on the ROTEM®.	After 22 hours, 46 hours and 70 hours
Maximum clot firmness (mm), -EXTEM, INTEM, FIBTEM and HEPTEM	Measured by thomboelastometry on the ROTEM®.	After 22 hours, 46 hours and 70 hours
Area under the curve, COL-test	Platelet function will be measured using Multiplate®.	After 22 hours and 70 hours
Area under the curve,- ADP, ASPI and TRAP-test.	Platelet function will be measured using Multiplate®.	After 22 hours, 46 hours and 70 hours
Time to maximum velocity (s), -EXTEM, INTEM, FIBTEM and HEPTEM	Measured by thomboelastometry on the ROTEM®.	After 22 hours, 46 hours and 70 hours
Maximum velocity (mm/min), -EXTEM, INTEM, FIBTEM and HEPTEM	Measured by thomboelastometry on the ROTEM®.	After 22 hours, 46 hours and 70 hours
Area under the curve, Clot stability test		After 22 hours, 46 hours and 70 hours
Area under the curve, Thrombin generation		After 22 hours, 46 hours and 70 hours

Other Outcome Measures

Outcome Measure	Time Frame
International normalized ratio	After 22 hours, 46 hours and 70 hours
APTT (activated partial thromboplastin time) in seconds	After 22 hours, 46 hours and 70 hours
Fibrinogen in mol/l	After 22 hours, 46 hours and 70 hours
Antithrombin in 10^3 int.units/l	After 22 hours, 46 hours and 70 hours
D-dimer in mg/l FEU	After 22 hours, 46 hours and 70 hours
Trombine time in seconds	After 22 hours, 46 hours and 70 hours

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Anni Norgaard Jeppesen, MD, Research Center of Emergency Medicine and Department of Anesthesiology and Intensive Care Medicine

Publications and helpful links

General Publications

• Jeppesen AN, Hvas AM, Duez CHV, Grejs AM, Ilkjaer S, Kirkegaard H. Prolonged targeted temperature management compromises thrombin generation: A randomised clinical trial. Resuscitation. 2017 Sep;118:126-132. doi: 10.1016/j.resuscitation.2017.06.004. Epub 2017 Jun 7.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: August 29, 2014
• First Submitted That Met QC Criteria: October 2, 2014
• First Posted (Estimate): October 7, 2014

Study Record Updates

• Last Update Posted (Estimate): March 29, 2016
• Last Update Submitted That Met QC Criteria: March 28, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Hypothermia; Heart Arrest; Thromboelastometry; Haemostasis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Body Temperature Changes; Heart Arrest; Hypothermia
• Other Study ID Numbers: PROID7005