Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hypothermia After Cardiac Arrest - Effects on Myocardial Function and Inflammatory Response. (IH3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03743584
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Søren Erik Pischke, Oslo University Hospital

Brief Summary:

The on-going randomized clinical trial TTM2 (Target Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest, NCT02908308) investigates if there is a difference in mortality, neurological function or quality of life in comatose survivors after out-of-hospital cardiac arrest if treated (Group A) at target temperature of 33 oC or (Group B) by avoiding fever during the first 24 h.

In this sub study, the effect of different target temperatures on cardiac and circulatory physiology is evaluated by echocardiography and pulmonary artery catheter. Tissue damage after cardiac arrest in part is caused by an activation of different parts of the inflammatory system (reperfusion injury). This study investigates the effect of temperature management on inflammation and the link to the circulatory effects.


Condition or disease Intervention/treatment Phase
Out of Hospital Cardiac Arrest Inflammatory Response Ischemia Reperfusion Injury Hypothermia Procedure: Targeted temperature management Procedure: Standard care, early treatment of fever Not Applicable

Detailed Description:

Hypothermia (HT) is used as an adjunctive treatment to improve outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA). Optimal temperature is debated and in the TTM-trial (Target Temperature Management study), which randomized to management at either 33 degrees C or 36 degrees C for 24h after return of spontaneous circulation (ROSC), no difference in mortality or neurological outcome was shown. The TTM-2-trial (Target Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest, NCT02908308) was initiated to investigate if there is a difference in mortality, neurological function or quality of life between target temperature of 33 degrees C or avoiding fever in comatose patients after out-of-hospital cardiac arrest and meet some of the critique that was raised against the TTM-trial regarding the speed of induction of hypothermia, that both groups were treated at different degrees of hypothermia and that both groups could have benefitted from this intervention.

This study is a prospective sub-study to the TTM-2 trial investigating the cardiac and hemodynamic effects of different target temperatures using echocardiography and pulmonary artery catheter (PAC). Data will be harvested and echocardiographic registration will be made during the target temperature phase, upon rewarming and after 48-72 hours. There will be a follow-up echocardiographic examination at 6 months from randomization.

Ischemia/reperfusion (I/R) injury is a key challenge in myocardial infarction and cardiac arrest. In this study most patients will experience myocardial infarction affecting the heart only, while all patients will experience cardiac arrest affecting the whole body. A major determinant of long-term outcome is the degree of cell death due to stop of blood supply during ischemia and aggravation of organ damage during reperfusion caused by innate immune activation. In this study we will address the importance of the innate immune system in determining outcome and the interplay and dependency with cardiac function.

Blood samples will be collected at the same time points as echocardiography registrations and collection of hemodynamic data and analyzed post study cessation.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: The clinical team responsible for the participant (physicians, nurses and others) and involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention and as temperature is a vital sign required for clinical care. Measures will be taken to ensure that the information about allocation will not disseminate beyond the immediate group of caregivers responsible for patient care. A blinded physician will evaluate the patient for Cardiac function at pre-specified time-Points after randomisation and make a statement on Cardiac function.
Primary Purpose: Treatment
Official Title: Hypothermia After Cardiac Arrest - Effects on Myocardial Function and Inflammatory Response.
Actual Study Start Date : November 8, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Targeted temperature management at 33°C
Cooling and temperature control at 33°C, according to the study protocol of the TTM2-trial
Procedure: Targeted temperature management
Target temperature management at 33°C

Active Comparator: Standard care, early treatment of fever
Standard of care and normothermia. If temperature 37,8 °C or above use of device for temperature control.
Procedure: Standard care, early treatment of fever
Standard of care with early treatment of fever




Primary Outcome Measures :
  1. Change in wall motion score [ Time Frame: 48 hours , 72 hours, 6 months ]
    Cardiac output

  2. Plasma concentration of inflammatory markers [ Time Frame: 48 hours , 72 hours, 6 months ]
    inflammatory markers to be specified (e.g. Complement system activation, pro-inflammatory cytokines like IL-6 expressed as nanogram/milliliter)


Secondary Outcome Measures :
  1. Association between inflammatory response and cardiac function [ Time Frame: 48 hours , 72 hours, 6 months ]
    Association of plasma concentration of inflammatory markers (nanogram/milliliter) and Cardiac output (liter/minute)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Included in the TTM2-trial and treated at the Intensive Care Unit at Rikshospitalet, Oslo
  • Out-of-hospital cardiac arrest of a presumed cardiac or unknown cause
  • Sustained ROSC - defined as 20 minutes with signs of circulation without the need for chest compressions.
  • Unconsciousness defined as not being able to obey verbal commands (FOUR-score motor response of <4) and no verbal response to pain after sustained ROSC.
  • Eligible for intensive care without restrictions or limitations
  • Inclusion within 180 minutes of ROSC

Exclusion Criteria:

  • Not included in the TTM2-trial
  • 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
  • Severe chronic obstructive pulmonary disorder (COPD) with long-term home oxygen therapy"

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03743584


Contacts
Layout table for location contacts
Contact: Simon Jakobsson, MD 004740495963 simjak@ous-hf.no
Contact: Andreas Espinoza, MD, PhD 004797699870 a.w.espinoza@studmed.uio.no

Locations
Layout table for location information
Norway
Oslo University Hospital Recruiting
Oslo, Norway, 0424
Contact: Simon Jakobsson, MD    +4723070000    simjak@ous-hf.no   
Contact: Søren Pischke, MD PhD    +4723070000    soepis@ous-hf.no   
Sponsors and Collaborators
Oslo University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Søren Pischke, MD, PhD Oslo University Hospital, Oslo, Norway

Layout table for additonal information
Responsible Party: Søren Erik Pischke, Principal Investigator, MD, PhD. Senior consultant, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT03743584     History of Changes
Other Study ID Numbers: 2018/1057 C
First Posted: November 16, 2018    Key Record Dates
Last Update Posted: November 27, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Søren Erik Pischke, Oslo University Hospital:
cardiac arrest
hypothermia, therapeutic
ischemia reperfusion injury
Innate Immune system

Additional relevant MeSH terms:
Layout table for MeSH terms
Ischemia
Heart Arrest
Hypothermia
Reperfusion Injury
Out-of-Hospital Cardiac Arrest
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Body Temperature Changes
Signs and Symptoms
Vascular Diseases
Postoperative Complications