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

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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

Tracking Information
First Submitted Date  ICMJE November 6, 2018
First Posted Date  ICMJE November 16, 2018
Last Update Posted Date November 27, 2018
Actual Study Start Date  ICMJE November 8, 2018
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
  • Change in wall motion score [ Time Frame: 48 hours , 72 hours, 6 months ]
    Cardiac output
  • 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03743584 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hypothermia After Cardiac Arrest - Effects on Myocardial Function and Inflammatory Response.
Official Title  ICMJE Hypothermia After Cardiac Arrest - Effects on Myocardial Function and Inflammatory Response.
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE
  • Out of Hospital Cardiac Arrest
  • Inflammatory Response
  • Ischemia Reperfusion Injury
  • Hypothermia
Intervention  ICMJE
  • Procedure: Targeted temperature management
    Target temperature management at 33°C
  • Procedure: Standard care, early treatment of fever
    Standard of care with early treatment of fever
Study Arms  ICMJE
  • Experimental: Targeted temperature management at 33°C
    Cooling and temperature control at 33°C, according to the study protocol of the TTM2-trial
    Intervention: Procedure: Targeted temperature management
  • 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.
    Intervention: Procedure: Standard care, early treatment of fever
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 13, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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"
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Simon Jakobsson, MD 004740495963 simjak@ous-hf.no
Contact: Andreas Espinoza, MD, PhD 004797699870 a.w.espinoza@studmed.uio.no
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03743584
Other Study ID Numbers  ICMJE 2018/1057 C
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Søren Erik Pischke, Oslo University Hospital
Study Sponsor  ICMJE Oslo University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Søren Pischke, MD, PhD Oslo University Hospital, Oslo, Norway
PRS Account Oslo University Hospital
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP