search
Back to results

Targeted Temperature Management After In-Hospital Cardiac Arrest (TTM36-IHCA)

Primary Purpose

Hypoxic Ischemic Encephalopathy

Status
Unknown status
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Arctic Sun®
Arcticgel™
Conventional antipyretic treatment
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoxic Ischemic Encephalopathy focused on measuring Targeted Temperature Management(TTM), in-hospital cardiac arrest(IHCA), restoration of spontaneous circulation(ROSC), unconsciousness, brain injury

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18-80 years
  • In-hospital cardiac arrest requiring chest compression for > 2 minutes
  • Sustained restoration of spontaneous circulation(ROSC) for > 20 minutes after cardiopulmonary resuscitation(CPR)
  • Unresponsive state(lack of meaningful response to verbal commands) for > 20 minutes after sustained ROSC
  • Informed consents from a patient's family member

Exclusion Criteria:

  • Unavailable TTM within 2 hours after ROSC
  • CPR duration > 30 minutes
  • Unwitnessed arrest with initial rhythm asystole
  • Under or planned for extracorporeal membrane oxygenation(ECMO)
  • Initial body temperature < 33 °C
  • Preexisting terminal illness with life expectancy <6 months
  • Pre-admission CPC score of 3-5
  • Pre-admission mRS score 4-6
  • Unresponsive(stupor or coma) before cardiac arrest
  • Suspected or confirmed cause of cardiac arrest is diseases of the central nervous system, such as stroke, brain tumor, or amyotrophic lateral sclerosis
  • Any condition in which direct skin surface cooling would be contraindicated, such as large burns, unhealed surgical wounds, decubitus ulcers, cellulitis, or other conditions with disrupted skin integrity
  • Active massive bleeding
  • Major surgery within last 48 hours
  • Cardiothoracic surgery within 14 days
  • Planned surgery within next 72 hours after ROSC
  • Enrolled in other clinical trials
  • Pregnant women
  • Do-not-resuscitate(DNR) state
  • Patients whose family or treating physicians refuse to join this study

Sites / Locations

  • Asan Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TTM-36

Conventional treatment

Arm Description

Participants assigned to TTM-36 Arm will be managed by Arcticgel™ and Arctic Sun® to maintain core temperatureTemperature at 36.0℃ for 72 hours. After targeted temperature management(TTM), Fever will be controlled for remaining 7 days by conventional antipyretic treatment. (Treat core temperature ≥ 38.3℃). A total of 40 participants will be enrolled.

Participants who are assigned to this Arm will be treated with conventional antipyretic treatment regarding the occurrence fever for 7 days.(Treat core temperature ≥ 38.3℃). A total of 20 participants will be enrolled.

Outcomes

Primary Outcome Measures

Combination of death and poor neurological function defined as a Cerebral Performance Category (CPC) score 3 to 5 at 180 days
Efficacy of targeted temperature management at 36.0℃(TTM-36) will be assessed by using Cerebral Performance Category(CPC) score. CPC score is the surrogate outcome for hypoxic-ischemic brain injury.

Secondary Outcome Measures

The CPC score 3 to 5 at day 7 and at day 30
The highest levels of serum neuron specific enolase(NSE) during the first 5 days
Unfavorable Electroencephalography(EEG) patterns
Generalized suppression(≤20 μV) Burst-suppression with generalized epileptiform activity Generalized periodic epileptiform discharges on a flat background No EEG reactivity Electrographical seizures Electrographical status epilepticus
Assessment of magnetic resonance imaging(MRI) at day 4
Total magnetic resonance imaging(MRI) scores The percentage of brain volume with Afferent Diffusion Coefficient(ADC) values < 650 x 10^-6mm^2/sec The percentage of brain volume with ADC values < 450 x 10^-6mm^2/sec Number of cerebral microbleeds
Modified Rankin Scale(mRS) score 4 to 6 at day 30 and at Day 180
All-cause mortality at day 30, at Day 180
Myoclonic or tonic-clonic seizures or status epilepticus(SE)
Neurological status estimated by the Seoul Neurosychological Screeninig Battery (SNSB) 2nd ed.
Attention: Digit span (forward), digit span (backward) Language & related function: Spontaneous speech, comprehension, repetition, reading, writing, finger naming, body part identification, right-left orientation, calculation; BNT (Boston Naming Test) Visuospatial: RCFT (Rey Complex Figure Test) copy score Memory: SVLT (Seoul Verbal Learning Test), RCFT (immediate recall, delayed recall, recognition) Frontal & executive function: COWAT (Controlled Oral Word Association Test), CWST (Color Word Stroop Test), DSC (Digit Symbol Coding), TMT (Trail making test) General cognitive index: MMSE (Mini Mental State Examination), CDR (Clinical Dementia Rating), GDS (Global Deterioration Scale) Activities of daily living (ADL): Barthel index
Other neurological evaluations
Depression: BDI (Beck Depression Inventory) Quality of life: SF-36 (Short-Form 36-item Health Survey) Activities of daily life: S-IADL (Seoul-Instrumental Activities of Daily Living) Psychiatric symptoms: NPI (Neuropsychiatric Inventory) Cognition: IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) Parkinsonism: UPDRS (Unified Parkinson's Disease Rating Scale) Ataxia: ICARS (International Cooperative Ataxia Rating Scale)
Assessment of follow-up MRI
Resting state functional MRI: Connectivity strength, proportional increase of connectivity strength on resting state Diffusion tensor imaging: Global mean diffusivity, gray matter mean diffusivity, white matter mean diffusivity , mean fractional anisotropy, proportional increase of white matter global fractional anisotropy, proportional increase of white matter global mean diffusivity High resolution T1-weighted imaging for MRI volumetric: Mean volume of the brain, mean volume of the gray matter of the brain, mean volume of the white matter of the brain, proportional increase of mean volume of the brain, proportional increase of mean volume of the gray matter, proportional increase of mean volume of the white matter Susceptibility-weighted imaging: Number of cerebral microbleeds

Full Information

First Posted
October 15, 2015
Last Updated
June 28, 2016
Sponsor
Asan Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT02578823
Brief Title
Targeted Temperature Management After In-Hospital Cardiac Arrest
Acronym
TTM36-IHCA
Official Title
Targeted Temperature Management at 36℃ After In-Hospital Cardiac Arrest Trial(TTM36-IHCA Trial): An Investigator-Initiated, Single-Center, Randomized, Controlled, Assessor-Blinded, Pilot Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
January 2016 (undefined)
Primary Completion Date
April 2018 (Anticipated)
Study Completion Date
April 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine whether targeted temperature management at 36.0˚C(TTM-36) in patients who remain unconscious after resuscitation from in-hospital cardiac arrest(IHCA) will reduce death and disability compared with fever control. For this purpose, the current pilot study will be undertaken to establish the feasibility, safety, and surrogate outcomes of hypoxic-ischemic brain injury in 60 patients who remain unconscious after resuscitation from IHCA. Eligible patients will be randomly assigned in a 2:1 ratio to either TTM-36(n=40) or conventional treatment group(n=20). Randomization will be performed with stratification according to initial rhythm (shockable vs. non-shockable).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxic Ischemic Encephalopathy
Keywords
Targeted Temperature Management(TTM), in-hospital cardiac arrest(IHCA), restoration of spontaneous circulation(ROSC), unconsciousness, brain injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TTM-36
Arm Type
Experimental
Arm Description
Participants assigned to TTM-36 Arm will be managed by Arcticgel™ and Arctic Sun® to maintain core temperatureTemperature at 36.0℃ for 72 hours. After targeted temperature management(TTM), Fever will be controlled for remaining 7 days by conventional antipyretic treatment. (Treat core temperature ≥ 38.3℃). A total of 40 participants will be enrolled.
Arm Title
Conventional treatment
Arm Type
Active Comparator
Arm Description
Participants who are assigned to this Arm will be treated with conventional antipyretic treatment regarding the occurrence fever for 7 days.(Treat core temperature ≥ 38.3℃). A total of 20 participants will be enrolled.
Intervention Type
Device
Intervention Name(s)
Arctic Sun®
Other Intervention Name(s)
Temperature Management System Model 5000
Intervention Description
Core temperature is maintained to 36℃ for 3 days by using the skin attached pad(Arcticgel™) and targeted temperature management(Arctic Sun®).
Intervention Type
Device
Intervention Name(s)
Arcticgel™
Other Intervention Name(s)
Hydrogel Coated Pad
Intervention Type
Procedure
Intervention Name(s)
Conventional antipyretic treatment
Intervention Description
Conventional antipyretic treatment for fever includes using of antipyretics, ice packs, circulating fan, and tepid bathing, etc.
Primary Outcome Measure Information:
Title
Combination of death and poor neurological function defined as a Cerebral Performance Category (CPC) score 3 to 5 at 180 days
Description
Efficacy of targeted temperature management at 36.0℃(TTM-36) will be assessed by using Cerebral Performance Category(CPC) score. CPC score is the surrogate outcome for hypoxic-ischemic brain injury.
Time Frame
day 180
Secondary Outcome Measure Information:
Title
The CPC score 3 to 5 at day 7 and at day 30
Time Frame
day 7, day 30
Title
The highest levels of serum neuron specific enolase(NSE) during the first 5 days
Time Frame
up to day 5
Title
Unfavorable Electroencephalography(EEG) patterns
Description
Generalized suppression(≤20 μV) Burst-suppression with generalized epileptiform activity Generalized periodic epileptiform discharges on a flat background No EEG reactivity Electrographical seizures Electrographical status epilepticus
Time Frame
day 0, day 4
Title
Assessment of magnetic resonance imaging(MRI) at day 4
Description
Total magnetic resonance imaging(MRI) scores The percentage of brain volume with Afferent Diffusion Coefficient(ADC) values < 650 x 10^-6mm^2/sec The percentage of brain volume with ADC values < 450 x 10^-6mm^2/sec Number of cerebral microbleeds
Time Frame
day 4
Title
Modified Rankin Scale(mRS) score 4 to 6 at day 30 and at Day 180
Time Frame
day 30, day 180
Title
All-cause mortality at day 30, at Day 180
Time Frame
up to day 180
Title
Myoclonic or tonic-clonic seizures or status epilepticus(SE)
Time Frame
up to day 7
Title
Neurological status estimated by the Seoul Neurosychological Screeninig Battery (SNSB) 2nd ed.
Description
Attention: Digit span (forward), digit span (backward) Language & related function: Spontaneous speech, comprehension, repetition, reading, writing, finger naming, body part identification, right-left orientation, calculation; BNT (Boston Naming Test) Visuospatial: RCFT (Rey Complex Figure Test) copy score Memory: SVLT (Seoul Verbal Learning Test), RCFT (immediate recall, delayed recall, recognition) Frontal & executive function: COWAT (Controlled Oral Word Association Test), CWST (Color Word Stroop Test), DSC (Digit Symbol Coding), TMT (Trail making test) General cognitive index: MMSE (Mini Mental State Examination), CDR (Clinical Dementia Rating), GDS (Global Deterioration Scale) Activities of daily living (ADL): Barthel index
Time Frame
day 180
Title
Other neurological evaluations
Description
Depression: BDI (Beck Depression Inventory) Quality of life: SF-36 (Short-Form 36-item Health Survey) Activities of daily life: S-IADL (Seoul-Instrumental Activities of Daily Living) Psychiatric symptoms: NPI (Neuropsychiatric Inventory) Cognition: IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) Parkinsonism: UPDRS (Unified Parkinson's Disease Rating Scale) Ataxia: ICARS (International Cooperative Ataxia Rating Scale)
Time Frame
day 180
Title
Assessment of follow-up MRI
Description
Resting state functional MRI: Connectivity strength, proportional increase of connectivity strength on resting state Diffusion tensor imaging: Global mean diffusivity, gray matter mean diffusivity, white matter mean diffusivity , mean fractional anisotropy, proportional increase of white matter global fractional anisotropy, proportional increase of white matter global mean diffusivity High resolution T1-weighted imaging for MRI volumetric: Mean volume of the brain, mean volume of the gray matter of the brain, mean volume of the white matter of the brain, proportional increase of mean volume of the brain, proportional increase of mean volume of the gray matter, proportional increase of mean volume of the white matter Susceptibility-weighted imaging: Number of cerebral microbleeds
Time Frame
day 30 & day 180
Other Pre-specified Outcome Measures:
Title
Safety of the targeted temperature management at 36.0℃(TTM-36)
Description
Safety will be assessed by the composite measurement below everyday during the first 7 days after cardiac arrest. Cardiac arrest after randomization Arrhythmia(ventricular fibrillation, ventricular tachycardia, atrial fibrillation, atrial flutter, tachycardia >130/min lasting more than 1 hour, and bradycardia <40/min lasting more than 1 hour) Pneumonia(pulmonary infiltration on the chest radiography and 2 or more of fever, leukocytosis, and purulent tracheobronchial secretions) Septic shock(sepsis-induced hypotension persisting despite adequate fluid resuscitation) Culture-proven infection Major bleeding(bleeding requiring more than 2 units of packed red blood cell over 2 hours, bleeding causing fatality, and symptomatic bleeding in critical organs) Shivering(the Bedside Shivering Assessment Scale 2-3)
Time Frame
up to day 7
Title
Feasibility
Description
2.5 subjects per month can be recruited At least 50% of all eligible patients can be recruited No more than 10% of all recruited subjects cross over from one modality to the other Complete follow-up in at least 90% of all recruited subjects
Time Frame
up to day 180

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18-80 years In-hospital cardiac arrest requiring chest compression for > 2 minutes Sustained restoration of spontaneous circulation(ROSC) for > 20 minutes after cardiopulmonary resuscitation(CPR) Unresponsive state(lack of meaningful response to verbal commands) for > 20 minutes after sustained ROSC Informed consents from a patient's family member Exclusion Criteria: Unavailable TTM within 2 hours after ROSC CPR duration > 30 minutes Unwitnessed arrest with initial rhythm asystole Under or planned for extracorporeal membrane oxygenation(ECMO) Initial body temperature < 33 °C Preexisting terminal illness with life expectancy <6 months Pre-admission CPC score of 3-5 Pre-admission mRS score 4-6 Unresponsive(stupor or coma) before cardiac arrest Suspected or confirmed cause of cardiac arrest is diseases of the central nervous system, such as stroke, brain tumor, or amyotrophic lateral sclerosis Any condition in which direct skin surface cooling would be contraindicated, such as large burns, unhealed surgical wounds, decubitus ulcers, cellulitis, or other conditions with disrupted skin integrity Active massive bleeding Major surgery within last 48 hours Cardiothoracic surgery within 14 days Planned surgery within next 72 hours after ROSC Enrolled in other clinical trials Pregnant women Do-not-resuscitate(DNR) state Patients whose family or treating physicians refuse to join this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sang-Beom Jeon, Dr
Phone
82-2-3010-3440
Email
sbjeonmd@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sang-Beom Jeon, Dr
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sang-Beom Jeon, Dr
Phone
82-2-3010-3440
Email
sbjeonmd@gmail.com

12. IPD Sharing Statement

Learn more about this trial

Targeted Temperature Management After In-Hospital Cardiac Arrest

We'll reach out to this number within 24 hrs