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Adjunct Targeted Temperature Management in Acute Severe Carbon Monoxide Poisoning

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ClinicalTrials.gov Identifier: NCT04975867
Recruitment Status : Recruiting
First Posted : July 26, 2021
Last Update Posted : December 16, 2021
Sponsor:
Collaborator:
National Research Foundation of Korea
Information provided by (Responsible Party):
Yong Sung Cha, Wonju Severance Christian Hospital

Tracking Information
First Submitted Date  ICMJE July 1, 2021
First Posted Date  ICMJE July 26, 2021
Last Update Posted Date December 16, 2021
Actual Study Start Date  ICMJE October 25, 2021
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 13, 2021)		 Main neurocognitive outcome [ Time Frame: At 6 months after CO poisoning ]
Global Deterioration Scale [range 1 - 7 (worst score)]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 30, 2021)
  • Neurocognitive outcome [ Time Frame: At 1 month after CO poisoning ]
    Global Deterioration Scale [range 1 - 7 (worst score)]
  • Cerebral Performance Category [ Time Frame: At 1 month and 6 months after CO poisoning ]
    Cerebral Performance Category [range 1 - 5 (worst score)]
  • modified Rankin scale [ Time Frame: At 1 month and 6 months after CO poisoning ]
    modified Rankin scale [range 0 - 6 (worst score)]
  • Glasgow outcome scale [ Time Frame: At 1 month and 6 months after CO poisoning ]
    Glasgow outcome scale [range 1 (worst score) - 5]
  • mini-mental status exam [ Time Frame: At 1 month and 6 months after CO poisoning ]
    mini-mental status exam
  • Korean version of the Modified Barthel Index [ Time Frame: At 1 month and 6 months after CO poisoning ]
    Korean version of the Modified Barthel Index
  • Mortality in intensive care unit [ Time Frame: Through study completion, an average of 6 months ]
    Number of participants with mortality in intensive care unit
  • Mortality in intensive care unit [ Time Frame: Through study completion, an average of 6 months ]
    Rate of participants with mortality in intensive care unit
  • In-hospital mortality [ Time Frame: Through study completion, an average of 6 months ]
    Number of participants with in-hospital mortality
  • In-hospital mortality [ Time Frame: Through study completion, an average of 6 months ]
    Rate of participants with in-hospital mortality
  • Mortality [ Time Frame: At 1, 3, and 6 months after CO poisoning ]
    Number of participants with all cause mortality
  • Mortality [ Time Frame: At 1, 3, and 6 months after CO poisoning ]
    Rate of participants with all cause mortality
  • Length of stay in intensive care unit and hospital [ Time Frame: Through study completion, an average of 6 months ]
    Length of stay in intensive care unit and hospital
  • Pneumonia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    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 [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    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 [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    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 [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    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 [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Number of participants with dropped heart rate indicated drug or interventions
  • Bradycardia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Rate of participants with dropped heart rate indicated drug or interventions
  • Hypokalemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Number of participants with serum K concentration <3.0 - 2.5 mmol/L
  • Hypokalemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Rate of participants with serum K concentration <3.0 - 2.5 mmol/L
  • Hyperkalemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Number of participants with serum K concentration >6.0 - 7.0 mmol/L
  • Hyperkalemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Rate of participants with serum K concentration >6.0 - 7.0 mmol/L
  • Hyperglycemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Number of participants with change (Insulin therapy initiated) in daily management from baseline for serum glucose
  • Hyperglycemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Rate of participants with change (Insulin therapy initiated) in daily management from baseline for serum glucose
  • Hypophosphatemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    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 [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    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 [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Number of participants with serum magnesium <0.9 - 0.7 mg/dL
  • Hypomagnesemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Rate of participants with serum magnesium <0.9 - 0.7 mg/dL
  • Prolonged prothrombin Time International Normalized Ratio [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Number of participants with >2.5 x upper limit of the normal range and bleeding
  • Prolonged prothrombin Time International Normalized Ratio [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Rate of participants with >2.5 x upper limit of the normal range and bleeding
  • Prolonged activated partial thromboplastin time [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Number of participants with >2.5 x upper limit of the normal range and bleeding
  • Prolonged activated partial thromboplastin time [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Rate of participants with >2.5 x upper limit of the normal range and bleeding
  • S100ß (serum) [ Time Frame: Within 14 days after CO exposure ]
    Concentration of S100ß (serum)
  • Neuronal specific enolase (serum) [ Time Frame: Within 14 days after CO exposure ]
    Concentration of neuronal specific enolase (serum)
  • Brain magnetic resonance image (MRI) [ Time Frame: Within 14 days after CO exposure ]
    Number of participants with brain injury in brain MRI
  • Brain magnetic resonance image (MRI) [ Time Frame: Within 14 days after CO exposure ]
    Rate of participants with brain injury in brain MRI
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2021)
  • Neurocognitive outcome [ Time Frame: At 1 month after CO poisoning ]
    Global Deterioration Scale [range 1 - 7 (worst score)]
  • Cerebral Performance Category [ Time Frame: At 1 month and 6 months after CO poisoning ]
    Cerebral Performance Category [range 1 - 5 (worst score)]
  • modified Rankin scale [ Time Frame: At 1 month and 6 months after CO poisoning ]
    modified Rankin scale [range 0 - 6 (worst score)]
  • Glasgow outcome scale [ Time Frame: At 1 month and 6 months after CO poisoning ]
    Glasgow outcome scale [range 1 (worst score) - 5]
  • mini-mental status exam [ Time Frame: At 1 month and 6 months after CO poisoning ]
    mini-mental status exam
  • Korean version of the Modified Barthel Index [ Time Frame: At 1 month and 6 months after CO poisoning ]
    Korean version of the Modified Barthel Index
  • Mortality in intensive care unit [ Time Frame: Through study completion, an average of 6 months ]
    Mortality in intensive care unit
  • In-hospital mortality [ Time Frame: Through study completion, an average of 6 months ]
    In-hospital mortality
  • Mortality [ Time Frame: At 1, 3, and 6 months after CO poisoning ]
    All cause mortality
  • Length of stay in intensive care unit and hospital [ Time Frame: Through study completion, an average of 6 months ]
    Length of stay in intensive care unit and hospital
  • Pneumonia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    The diagnosis of pneumonia 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 [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Shock is diagnosed when a vasopressor is needed to resuscitate the patient and lactate levels exceeded 2.0 mmol/L.
  • Bradycardia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Dropped blood pressure and drug or interventions indicated
  • Hypokalemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Serum K concentration <3.0 - 2.5 mmol/L
  • Hyperkalemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Serum K concentration >6.0 - 7.0 mmol/L
  • Hyperglycemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Change (Insulin therapy initiated) in daily management from baseline for serum glucose
  • Hypophosphatemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    A disorder characterized by laboratory test results that indicate a low concentration of phosphates in the blood and indicated replacement therapy
  • Hypomagnesemia [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    Serum magnesium <0.9 - 0.7 mg/dL
  • Prolonged prothrombin Time International Normalized Ratio [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    >2.5 x upper limit of the normal range and bleeding
  • Prolonged activated partial thromboplastin time [ Time Frame: During the intervention (therapeutic hypothermia or normothermia) period (72 hours) ]
    >2.5 x upper limit of the normal range and bleeding
  • S100ß (serum) [ Time Frame: Within 14 days after CO exposure ]
    S100ß (serum)
  • Neuronal specific enolase (serum) [ Time Frame: Within 14 days after CO exposure ]
    Neuronal specific enolase (serum)
  • Brain magnetic resonance image (MRI) [ Time Frame: Within 14 days after CO exposure ]
    Brain injury in brain MRI
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjunct Targeted Temperature Management in Acute Severe Carbon Monoxide Poisoning
Official Title  ICMJE Targeted Temperature Management Combined With Hyperbaric Oxygen Therapy in Acute Severe Carbon Monoxide Poisoning: Multicenter Randomized Controlled Clinical Trial (TTM-COHB Trial)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
Assessors of neurocognitive outcomes at 1 and 6 months after CO exposure will be blinded to the allocated treatment group.
Primary Purpose: Treatment
Condition  ICMJE
  • Carbon Monoxide Poisoning
  • Neurologic Sequelae
  • Hypothermia
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • 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.
    Intervention: Other: Targeted therapeutic hypothermia
  • 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.
    Intervention: Other: Targeted therapeutic normothermia
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 13, 2021)		 46
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2025
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yong Sung Cha, MD +82-33-741-1615 emyscha@yonsei.ac.kr
Contact: Yoonsuk Lee, MD +82-33-741-1133 yslee524@gmail.com
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04975867
Other Study ID Numbers  ICMJE TTM-COHB trial
CR220011 ( Other Identifier: Wonju Severance Christian Hospital )
2021-04-043 ( Other Identifier: Inha University Hospital )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Yong Sung Cha, Wonju Severance Christian Hospital
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Wonju Severance Christian Hospital
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Research Foundation of Korea
Investigators  ICMJE
Principal Investigator: Yong Sung Cha, MD Wonju Severance Christian Hospital
PRS Account Wonju Severance Christian Hospital
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP