Targeted Temperature Management After In-Hospital Cardiac Arrest

Asan Medical Center60 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Hypoxic Ischemic Encephalopathy

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: day 180

Secondary Outcomes

The CPC score 3 to 5 at day 7 and at day 30

Time frame: day 7, day 30

The highest levels of serum neuron specific enolase(NSE) during the first 5 days

Time frame: up to day 5

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

Time frame: day 0, day 4

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

Time frame: day 4

Modified Rankin Scale(mRS) score 4 to 6 at day 30 and at Day 180

Time frame: day 30, day 180

All-cause mortality at day 30, at Day 180

Time frame: up to day 180

Myoclonic or tonic-clonic seizures or status epilepticus(SE)

Time frame: up to day 7

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

Time frame: day 180

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)

Time frame: day 180

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

Time frame: day 30 & day 180

Targeted Temperature Management After In-Hospital Cardiac Arrest

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts