Out of Hospital Cardiac ArrestIH3NCT03743584
Hypothermia After Cardiac Arrest - Effects on Myocardial Function and Inflammatory Response.
A study testing Targeted temperature management in people with Out of Hospital Cardiac Arrest and Inflammatory Response, run by Oslo University Hospital at 1 site in Norway.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Out of Hospital Cardiac Arrest, Inflammatory Response, Ischemia Reperfusion Injury
- What is being tested?
- Targeted temperature management
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteNorway
- Study dates
- 8 Nov 2018to 20 Jul 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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"
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Out of Hospital Cardiac Arrest, Inflammatory Response, Ischemia Reperfusion Injury, Hypothermia
- Being tested
- Targeted temperature management, Standard care, early treatment of fever
- Keywords
- cardiac arrest, hypothermia, therapeutic, ischemia reperfusion injury, Innate Immune system
- Medical subject headings
- Out-of-Hospital Cardiac Arrest, Reperfusion Injury, Hypothermia, Heart Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted temperature managementProcedure or surgery
Target temperature management at 33°C
Standard care, early treatment of feverProcedure or surgery
Standard of care with early treatment of fever
| Study group | Role | What they receive |
|---|---|---|
| Targeted temperature management at 33°C | Experimental | Cooling and temperature control at 33°C, according to the study protocol of the TTM2-trial Receives: Procedure: Targeted temperature management |
| Standard care, early treatment of fever | Active comparator | Standard of care and normothermia. If temperature 37,8 °C or above use of device for temperature control. Receives: Procedure: Standard care, early treatment of fever |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in wall motion score
Cardiac output
Measured: 48 hours , 72 hours, 6 months
Plasma concentration of inflammatory markers
inflammatory markers to be specified (e.g. Complement system activation, pro-inflammatory cytokines like IL-6 expressed as nanogram/milliliter)
Measured: 48 hours , 72 hours, 6 months
Secondary outcomes (1)
Association between inflammatory response and cardiac function
Association of plasma concentration of inflammatory markers (nanogram/milliliter) and Cardiac output (liter/minute)
Measured: 48 hours , 72 hours, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2018
- Study start8 Nov 2018
- Primary completion20 Jul 2020
- Study completion20 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Out of Hospital Cardiac ArrestStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Søren Erik Pischke, Oslo University Hospital
- Investigators
- Søren Pischke, MD, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03743584
- Sponsor's protocol ID
- 2018/1057 C
- Acronym
- IH3
- Status last verified
- Sep 2021
- First submitted
- 6 Nov 2018
- Last updated
- 20 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypothermia After Cardiac Arrest - Effects on Myocardial Function and Inflammatory Response.
- ClinicalTrials.gov ID
- NCT03743584
- Acronym / sponsor ID
- IH3 / 2018/1057 C
- Conditions
- Out of Hospital Cardiac Arrest, Inflammatory Response, Ischemia Reperfusion Injury, Hypothermia
- Keywords
- cardiac arrest, hypothermia, therapeutic, ischemia reperfusion injury, Innate Immune system
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Study start
- 8 Nov 2018 (actual)
- Primary completion
- 20 Jul 2020 (actual)
- Study completion
- 20 Jul 2020 (actual)
- First posted
- 16 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Targeted temperature management at 33°C | Experimental | Procedure: Targeted temperature managementCooling and temperature control at 33°C, according to the study protocol of the TTM2-trial |
| Standard care, early treatment of fever | Active comparator | Procedure: Standard care, early treatment of feverStandard of care and normothermia. If temperature 37,8 °C or above use of device for temperature control. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Targeted temperature managementTarget temperature management at 33°C | Procedure or surgery | Targeted temperature management at 33°C |
| Standard care, early treatment of feverStandard of care with early treatment of fever | Procedure or surgery | Standard care, early treatment of fever |
Primary outcome
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)
1 secondary outcome
Association between inflammatory response and cardiac function
Time frame: 48 hours , 72 hours, 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Søren Pischke, MD, PhD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Targeted temperature management in people with Out of Hospital Cardiac Arrest and Inflammatory Response, run by Oslo University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in wall motion score (time frame: 48 hours , 72 hours, 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2021.