Targeted Temperature Management After In-Hospital Cardiac Arrest

Hypoxic Ischemic Encephalopathy Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02578823
• Other study ID #: 2015-1071
• Status: Recruiting
• Phase: N/A
• First received: October 15, 2015
• Last updated: June 28, 2016
• Start date: January 2016
• Est. completion date: April 2018

Study information

• Verified date: June 2016
• Source: Asan Medical Center
• Contact: Sang-Beom Jeon, Dr
• Phone: 82-2-3010-3440
• Email: sbjeonmd[@]gmail.com
• Is FDA regulated: No
• Health authority: Korea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Heart Arrest
• Hypoxia-Ischemia, Brain
• Hypoxic Ischemic Encephalopathy

Intervention

Device:
• Arctic Sun®
Core temperature is maintained to 36? for 3 days by using the skin attached pad(Arcticgel™) and targeted temperature management(Arctic Sun®).
• Arcticgel™

Procedure:
• Conventional antipyretic treatment
Conventional antipyretic treatment for fever includes using of antipyretics, ice packs, circulating fan, and tepid bathing, etc.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety of the targeted temperature management at 36.0?(TTM-36)	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)	up to day 7	Yes
Other	Feasibility	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	up to day 180	No
Primary	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.	day 180	Yes
Secondary	The CPC score 3 to 5 at day 7 and at day 30		day 7, day 30	Yes
Secondary	The highest levels of serum neuron specific enolase(NSE) during the first 5 days		up to day 5	Yes
Secondary	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	day 0, day 4	Yes
Secondary	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	day 4	Yes
Secondary	Modified Rankin Scale(mRS) score 4 to 6 at day 30 and at Day 180		day 30, day 180	Yes
Secondary	All-cause mortality at day 30, at Day 180		up to day 180	Yes
Secondary	Myoclonic or tonic-clonic seizures or status epilepticus(SE)		up to day 7	Yes
Secondary	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	day 180	Yes
Secondary	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)	day 180	Yes
Secondary	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	day 30 & day 180	Yes