Back to resultsAdjunct Targeted Temperature Management in Acute Severe Carbon Monoxide Poisoning
Primary Purpose
Carbon Monoxide Poisoning, Neurologic Sequelae, Hypothermia
Status
Recruiting
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Targeted therapeutic hypothermia
Targeted therapeutic normothermia
Sponsored by
About this trial
This is an interventional treatment trial for Carbon Monoxide Poisoning
Eligibility Criteria
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)
Sites / Locations
- Wonju Severance Christian HospitalRecruiting
- Inha University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Hypothermia group
Normothermia group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Main neurocognitive outcome
Global Deterioration Scale [range 1 - 7 (worst score)]
Secondary Outcome Measures
Neurocognitive outcome
Global Deterioration Scale [range 1 - 7 (worst score)]
Cerebral Performance Category
Cerebral Performance Category [range 1 - 5 (worst score)]
modified Rankin scale
modified Rankin scale [range 0 - 6 (worst score)]
Glasgow outcome scale
Glasgow outcome scale [range 1 (worst score) - 5]
mini-mental status exam
mini-mental status exam
Korean version of the Modified Barthel Index
Korean version of the Modified Barthel Index
Mortality in intensive care unit
Number of participants with mortality in intensive care unit
Mortality in intensive care unit
Rate of participants with mortality in intensive care unit
In-hospital mortality
Number of participants with in-hospital mortality
In-hospital mortality
Rate of participants with in-hospital mortality
Mortality
Number of participants with all cause mortality
Mortality
Rate of participants with all cause mortality
Length of stay in intensive care unit and hospital
Length of stay in intensive care unit and hospital
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.
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.
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.
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.
Bradycardia
Number of participants with dropped heart rate indicated drug or interventions
Bradycardia
Rate of participants with dropped heart rate indicated drug or interventions
Hypokalemia
Number of participants with serum K concentration <3.0 - 2.5 mmol/L
Hypokalemia
Rate of participants with serum K concentration <3.0 - 2.5 mmol/L
Hyperkalemia
Number of participants with serum K concentration >6.0 - 7.0 mmol/L
Hyperkalemia
Rate of participants with serum K concentration >6.0 - 7.0 mmol/L
Hyperglycemia
Number of participants with change (Insulin therapy initiated) in daily management from baseline for serum glucose
Hyperglycemia
Rate of participants with change (Insulin therapy initiated) in daily management from baseline for serum glucose
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
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
Hypomagnesemia
Number of participants with serum magnesium <0.9 - 0.7 mg/dL
Hypomagnesemia
Rate of participants with serum magnesium <0.9 - 0.7 mg/dL
Prolonged prothrombin Time International Normalized Ratio
Number of participants with >2.5 x upper limit of the normal range and bleeding
Prolonged prothrombin Time International Normalized Ratio
Rate of participants with >2.5 x upper limit of the normal range and bleeding
Prolonged activated partial thromboplastin time
Number of participants with >2.5 x upper limit of the normal range and bleeding
Prolonged activated partial thromboplastin time
Rate of participants with >2.5 x upper limit of the normal range and bleeding
S100ß (serum)
Concentration of S100ß (serum)
Neuronal specific enolase (serum)
Concentration of neuronal specific enolase (serum)
Brain magnetic resonance image (MRI)
Number of participants with brain injury in brain MRI
Brain magnetic resonance image (MRI)
Rate of participants with brain injury in brain MRI
Full Information
NCT ID
NCT04975867
First Posted
July 1, 2021
Last Updated
May 1, 2023
Sponsor
Wonju Severance Christian Hospital
Collaborators
National Research Foundation of Korea
1. Study Identification
Unique Protocol Identification Number
NCT04975867
Brief Title
Adjunct Targeted Temperature Management in Acute Severe Carbon Monoxide Poisoning
Official Title
Targeted Temperature Management Combined With Hyperbaric Oxygen Therapy in Acute Severe Carbon Monoxide Poisoning: Multicenter Randomized Controlled Clinical Trial (TTM-COHB Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 25, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wonju Severance Christian Hospital
Collaborators
National Research Foundation of Korea
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carbon Monoxide Poisoning, Neurologic Sequelae, Hypothermia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Assessors of neurocognitive outcomes at 1 and 6 months after CO exposure will be blinded to the allocated treatment group.
Allocation
Randomized
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Hypothermia group
Arm Type
Experimental
Arm Description
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.
Arm Title
Normothermia group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Targeted therapeutic hypothermia
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Targeted therapeutic normothermia
Intervention Description
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.
Primary Outcome Measure Information:
Title
Main neurocognitive outcome
Description
Global Deterioration Scale [range 1 - 7 (worst score)]
Time Frame
At 6 months after CO poisoning
Secondary Outcome Measure Information:
Title
Neurocognitive outcome
Description
Global Deterioration Scale [range 1 - 7 (worst score)]
Time Frame
At 1 month after CO poisoning
Title
Cerebral Performance Category
Description
Cerebral Performance Category [range 1 - 5 (worst score)]
Time Frame
At 1 month and 6 months after CO poisoning
Title
modified Rankin scale
Description
modified Rankin scale [range 0 - 6 (worst score)]
Time Frame
At 1 month and 6 months after CO poisoning
Title
Glasgow outcome scale
Description
Glasgow outcome scale [range 1 (worst score) - 5]
Time Frame
At 1 month and 6 months after CO poisoning
Title
mini-mental status exam
Description
mini-mental status exam
Time Frame
At 1 month and 6 months after CO poisoning
Title
Korean version of the Modified Barthel Index
Description
Korean version of the Modified Barthel Index
Time Frame
At 1 month and 6 months after CO poisoning
Title
Mortality in intensive care unit
Description
Number of participants with mortality in intensive care unit
Time Frame
Through study completion, an average of 6 months
Title
Mortality in intensive care unit
Description
Rate of participants with mortality in intensive care unit
Time Frame
Through study completion, an average of 6 months
Title
In-hospital mortality
Description
Number of participants with in-hospital mortality
Time Frame
Through study completion, an average of 6 months
Title
In-hospital mortality
Description
Rate of participants with in-hospital mortality
Time Frame
Through study completion, an average of 6 months
Title
Mortality
Description
Number of participants with all cause mortality
Time Frame
At 1, 3, and 6 months after CO poisoning
Title
Mortality
Description
Rate of participants with all cause mortality
Time Frame
At 1, 3, and 6 months after CO poisoning
Title
Length of stay in intensive care unit and hospital
Description
Length of stay in intensive care unit and hospital
Time Frame
Through study completion, an average of 6 months
Title
Pneumonia
Description
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.
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Pneumonia
Description
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.
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Shock
Description
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.
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Shock
Description
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.
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Bradycardia
Description
Number of participants with dropped heart rate indicated drug or interventions
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Bradycardia
Description
Rate of participants with dropped heart rate indicated drug or interventions
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hypokalemia
Description
Number of participants with serum K concentration <3.0 - 2.5 mmol/L
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hypokalemia
Description
Rate of participants with serum K concentration <3.0 - 2.5 mmol/L
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hyperkalemia
Description
Number of participants with serum K concentration >6.0 - 7.0 mmol/L
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hyperkalemia
Description
Rate of participants with serum K concentration >6.0 - 7.0 mmol/L
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hyperglycemia
Description
Number of participants with change (Insulin therapy initiated) in daily management from baseline for serum glucose
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hyperglycemia
Description
Rate of participants with change (Insulin therapy initiated) in daily management from baseline for serum glucose
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hypophosphatemia
Description
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
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hypophosphatemia
Description
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
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hypomagnesemia
Description
Number of participants with serum magnesium <0.9 - 0.7 mg/dL
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Hypomagnesemia
Description
Rate of participants with serum magnesium <0.9 - 0.7 mg/dL
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Prolonged prothrombin Time International Normalized Ratio
Description
Number of participants with >2.5 x upper limit of the normal range and bleeding
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Prolonged prothrombin Time International Normalized Ratio
Description
Rate of participants with >2.5 x upper limit of the normal range and bleeding
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Prolonged activated partial thromboplastin time
Description
Number of participants with >2.5 x upper limit of the normal range and bleeding
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
Prolonged activated partial thromboplastin time
Description
Rate of participants with >2.5 x upper limit of the normal range and bleeding
Time Frame
During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Title
S100ß (serum)
Description
Concentration of S100ß (serum)
Time Frame
Within 14 days after CO exposure
Title
Neuronal specific enolase (serum)
Description
Concentration of neuronal specific enolase (serum)
Time Frame
Within 14 days after CO exposure
Title
Brain magnetic resonance image (MRI)
Description
Number of participants with brain injury in brain MRI
Time Frame
Within 14 days after CO exposure
Title
Brain magnetic resonance image (MRI)
Description
Rate of participants with brain injury in brain MRI
Time Frame
Within 14 days after CO exposure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yong Sung Cha, MD
Phone
+82-33-741-1615
Email
emyscha@yonsei.ac.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Yoonsuk Lee, MD
Phone
+82-33-741-1133
Email
yslee524@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yong Sung Cha, MD
Organizational Affiliation
Wonju Severance Christian Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wonju Severance Christian Hospital
City
Wonju
State/Province
Gangwon
ZIP/Postal Code
26426
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yong Sung Cha, MD
Phone
+82-33-741-1615
Email
emyscha@yonsei.ac.kr
First Name & Middle Initial & Last Name & Degree
Yoonsuk Lee, MD
Phone
+82-33-741-1133
Email
yslee524@gmail.com
First Name & Middle Initial & Last Name & Degree
Yong Sung Cha, MD
First Name & Middle Initial & Last Name & Degree
Yoonsuk Lee, MD
First Name & Middle Initial & Last Name & Degree
Hyun Kim, MD
First Name & Middle Initial & Last Name & Degree
Sang-yeol Yong, MD
Facility Name
Inha University Hospital
City
Incheon
ZIP/Postal Code
22332
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jin Hui Paik, MD
Phone
+82-32-890-2310
Email
riven2ne@inha.ac.kr
First Name & Middle Initial & Last Name & Degree
Soo Kang, MD
Phone
+82-32-890-2310
Email
dr_peace@naver.com
First Name & Middle Initial & Last Name & Degree
Jin Hui Paik, MD
First Name & Middle Initial & Last Name & Degree
Soo Kang, MD
First Name & Middle Initial & Last Name & Degree
Tae Kyu Ahn, MD
First Name & Middle Initial & Last Name & Degree
Young Ho Seo, MD
First Name & Middle Initial & Last Name & Degree
Kyung-Lim Joa, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
32697512
Citation
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.
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Adjunct Targeted Temperature Management in Acute Severe Carbon Monoxide Poisoning
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