Adjunct Targeted Temperature Management in Acute Severe Carbon Monoxide Poisoning

Targeted Temperature Management Combined With Hyperbaric Oxygen Therapy in Acute Severe Carbon Monoxide Poisoning: Multicenter Randomized Controlled Clinical Trial (TTM-COHB Trial)

This randomized trial will investigate important neurocognitive clinical outcomes of patients with acute severe carbon monoxide poisoning (ASCOP) randomized to receive either therapeutic hypothermia or normothermia combined with hyperbaric oxygen therapy (HBO).

Study Overview

• Status: Completed
• Conditions: Hypothermia; Carbon Monoxide Poisoning; Neurologic Sequelae
• Intervention / Treatment: Other: Targeted therapeutic hypothermia; Other: Targeted therapeutic normothermia

Detailed Description

CO-poisoned patients are identified by medical history and carboxyhemoglobin (CO-Hb) value >5% (>10% in smokers). Patients presenting with acute CO poisoning will receive one HBO. ASCOP is defined as mental status showing response to painful stimulus or unresponsiveness requiring intubation for airway protection and ventilation support at the emerency department, and persistence of depressed mental status despite the HBO. After HBO treatment, eligible patients who provide consent will be randomly allocated to receive hypothermia, or normothermia treatment administered in a open label fashion except for blinding of outcome assessor.

Outcome measures will be administered at 1 month and 6 months after CO exposure. In addition, we will examine the differences in serum markers and mortality between the hypothermia and normothermia groups.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Korea
  • Gangwon-do
    • Wŏnju, Gangwon-do, South Korea, 26426
      • Wonju Severance Christian Hospital
  • Incheon
    • Incheon, Incheon, South Korea, 22332
      • Inha University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 19 years.
• Patients who received HBO within 24 hours for acute CO poisoning.
• Patients who meet the definition of ASCOP (Patients incapable verbal obey after HBO).
• Signed informed consent prior to study entry.

Exclusion Criteria:

• Cardiac arrest before HBO
• Previous neurocognitive disorders
• Life-threatening underlying disease (ex: advanced cancer)
• Evidence of co-ingestion of sedative or hypnotics confirmed by intravenous flumazenil administration or history taking at the emergency department
• Absolute contraindication for TH (active severe bleeding and profound shock not controlled by vasoactive drugs)
• No admission
• The significant co-ingested drug levels, which are alter the consciousness, is confirmed from the drug analysis lab
• Pregnancy
• Burns
• More than moderate burn or Inhalation burn
• Burns complicated by other trauma
• Electrical burn
• Burns in high risk patients (Patients with chronic underlying diseases (i.e DM, ESRD, liver cirrhosis, etc) which may cause delays or aggravate the wound healing)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypothermia group; Hypothermia group is then performed at a body temperature of 33±0.5 °C during 24 h using a surface cooling device as soon as possible after the HBO and research consent. After therapeutic hypothermia ended, rewarming is done slowly between 0.2℃ - 0.5℃/h for 12 hours. After rewarming, it will be held at 36.5 ℃ for 36 hours.	Other: Targeted therapeutic hypothermia; Targeted therapeutic hypothermia is then performed at a body temperature of 33±0.5 °C during 24 h using a surface cooling device as soon as possible after the HBO and research consent. After TH ended, rewarming is done slowly between 0.2℃ - 0.5℃/h for 12 hours. After rewarming, it will be held at 36.5 ℃ for 36 hours.
Active Comparator: Normothermia group; For normothermia group, it will be held at 36.5±0.5 ℃ for 72 hours using a surface cooling device after the HBO and research consent.	Other: Targeted therapeutic normothermia; Targeted therapeutic normothermia will be held at 36.5±0.5 ℃ for 72 hours using a surface cooling device after the HBO and research consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main neurocognitive outcome	Global Deterioration Scale [range 1 - 7 (worst score)]	At 6 months after CO poisoning

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive outcome	Global Deterioration Scale [range 1 - 7 (worst score)]	At 1 month after CO poisoning
Cerebral Performance Category	Cerebral Performance Category [range 1 - 5 (worst score)]	At 1 month and 6 months after CO poisoning
modified Rankin scale	modified Rankin scale [range 0 - 6 (worst score)]	At 1 month and 6 months after CO poisoning
Glasgow outcome scale	Glasgow outcome scale [range 1 (worst score) - 5]	At 1 month and 6 months after CO poisoning
mini-mental status exam	mini-mental status exam	At 1 month and 6 months after CO poisoning
Korean version of the Modified Barthel Index	Korean version of the Modified Barthel Index	At 1 month and 6 months after CO poisoning
Mortality in intensive care unit	Number of participants with mortality in intensive care unit	Through study completion, an average of 6 months
Mortality in intensive care unit	Rate of participants with mortality in intensive care unit	Through study completion, an average of 6 months
In-hospital mortality	Number of participants with in-hospital mortality	Through study completion, an average of 6 months
In-hospital mortality	Rate of participants with in-hospital mortality	Through study completion, an average of 6 months
Mortality	Number of participants with all cause mortality	At 1, 3, and 6 months after CO poisoning
Mortality	Rate of participants with all cause mortality	At 1, 3, and 6 months after CO poisoning
Length of stay in intensive care unit and hospital	Length of stay in intensive care unit and hospital	Through study completion, an average of 6 months
Pneumonia	Number of participants with the diagnosis of pneumonia. Diagnosis is established when the following two criteria are met: 1) the appearance of a new infiltrate or consolidation on chest x-ray; and 2) leukocytosis, or leukopenia, or the significant presence of meaningful bacteria in a sputum culture with the absence of other infections.	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Pneumonia	Rate of participants with the diagnosis of pneumonia. Diagnosis is established when the following two criteria are met: 1) the appearance of a new infiltrate or consolidation on chest x-ray; and 2) leukocytosis, or leukopenia, or the significant presence of meaningful bacteria in a sputum culture with the absence of other infections.	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Shock	Number of participants with shock. Diagnosis is diagnosed when a vasopressor is needed to resuscitate the patient and lactate levels exceeded 2.0 mmol/L.	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Shock	Rate of participants with shock. Diagnosis is diagnosed when a vasopressor is needed to resuscitate the patient and lactate levels exceeded 2.0 mmol/L.	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Bradycardia	Number of participants with dropped heart rate indicated drug or interventions	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Bradycardia	Rate of participants with dropped heart rate indicated drug or interventions	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hypokalemia	Number of participants with serum K concentration <3.0 - 2.5 mmol/L	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hypokalemia	Rate of participants with serum K concentration <3.0 - 2.5 mmol/L	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hyperkalemia	Number of participants with serum K concentration >6.0 - 7.0 mmol/L	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hyperkalemia	Rate of participants with serum K concentration >6.0 - 7.0 mmol/L	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hyperglycemia	Number of participants with change (Insulin therapy initiated) in daily management from baseline for serum glucose	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hyperglycemia	Rate of participants with change (Insulin therapy initiated) in daily management from baseline for serum glucose	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hypophosphatemia	Number of participants with a disorder characterized by laboratory test results that indicate a low concentration of phosphates in the blood and indicated replacement therapy	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hypophosphatemia	Rate of participants with a disorder characterized by laboratory test results that indicate a low concentration of phosphates in the blood and indicated replacement therapy	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hypomagnesemia	Number of participants with serum magnesium <0.9 - 0.7 mg/dL	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Hypomagnesemia	Rate of participants with serum magnesium <0.9 - 0.7 mg/dL	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Prolonged prothrombin Time International Normalized Ratio	Number of participants with >2.5 x upper limit of the normal range and bleeding	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Prolonged prothrombin Time International Normalized Ratio	Rate of participants with >2.5 x upper limit of the normal range and bleeding	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Prolonged activated partial thromboplastin time	Number of participants with >2.5 x upper limit of the normal range and bleeding	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Prolonged activated partial thromboplastin time	Rate of participants with >2.5 x upper limit of the normal range and bleeding	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
S100ß (serum)	Concentration of S100ß (serum)	Within 14 days after CO exposure
Neuronal specific enolase (serum)	Concentration of neuronal specific enolase (serum)	Within 14 days after CO exposure
Brain magnetic resonance image (MRI)	Number of participants with brain injury in brain MRI	Within 14 days after CO exposure
Brain magnetic resonance image (MRI)	Rate of participants with brain injury in brain MRI	Within 14 days after CO exposure

Collaborators and Investigators

• Sponsor: Wonju Severance Christian Hospital
• Collaborators: National Research Foundation of Korea
• Investigators: Principal Investigator: Yong Sung Cha, MD, Wonju Severance Christian Hospital

Publications and helpful links

General Publications

• Kim SJ, Thom SR, Kim H, Hwang SO, Lee Y, Park EJ, Lee SJ, Cha YS. Effects of Adjunctive Therapeutic Hypothermia Combined With Hyperbaric Oxygen Therapy in Acute Severe Carbon Monoxide Poisoning. Crit Care Med. 2020 Aug;48(8):e706-e714. doi: 10.1097/CCM.0000000000004419.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2021
• Primary Completion (Actual): November 7, 2025
• Study Completion (Actual): November 7, 2025

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Poisoning; Body Temperature Changes; Gas Poisoning; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypothermia; Carbon Monoxide Poisoning; Therapeutics; Cryotherapy; Hypothermia, Induced
• Other Study ID Numbers: TTM-COHB trial; CR220011 (Other Identifier: Wonju Severance Christian Hospital); 2021-04-043 (Other Identifier: Inha University Hospital)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No