Adjunct Targeted Temperature Management in Acute Severe Carbon Monoxide Poisoning

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Carbon Monoxide Poisoning, Neurologic Sequelae, Hypothermia

Intervention / Treatment
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* Other: Targeted therapeutic hypothermia
* Other: Targeted therapeutic normothermia


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypothermia group<br>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<br>* 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.<br>|
| Active Comparator: Normothermia group<br>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<br>* 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.<br>|

What is the study measuring?
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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 |