Adjunct Targeted Temperature Management in Acute Severe Carbon Monoxide Poisoning

Hypothermia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04975867
• Other study ID #: TTM-COHB trial
• Secondary ID: CR2200112021-04-
• Status: Recruiting
• Phase: N/A
• Start date: October 25, 2021
• Est. completion date: July 31, 2025

Study information

• Verified date: May 2023
• Source: Wonju Severance Christian Hospital
• Contact: Yong Sung Cha, MD
• Phone: +82-33-741-1615
• Email: emyscha[@]yonsei.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: July 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carbon Monoxide Poisoning
• Hypothermia
• Poisoning

Intervention

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.
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Wonju Severance Christian Hospital	Wonju	Gangwon

Sponsors (2)

Lead Sponsor	Collaborator
Wonju Severance Christian Hospital	National Research Foundation of Korea

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Main neurocognitive outcome	Global Deterioration Scale [range 1 - 7 (worst score)]	At 6 months after CO poisoning
Secondary	Neurocognitive outcome	Global Deterioration Scale [range 1 - 7 (worst score)]	At 1 month after CO poisoning
Secondary	Cerebral Performance Category	Cerebral Performance Category [range 1 - 5 (worst score)]	At 1 month and 6 months after CO poisoning
Secondary	modified Rankin scale	modified Rankin scale [range 0 - 6 (worst score)]	At 1 month and 6 months after CO poisoning
Secondary	Glasgow outcome scale	Glasgow outcome scale [range 1 (worst score) - 5]	At 1 month and 6 months after CO poisoning
Secondary	mini-mental status exam	mini-mental status exam	At 1 month and 6 months after CO poisoning
Secondary	Korean version of the Modified Barthel Index	Korean version of the Modified Barthel Index	At 1 month and 6 months after CO poisoning
Secondary	Mortality in intensive care unit	Number of participants with mortality in intensive care unit	Through study completion, an average of 6 months
Secondary	Mortality in intensive care unit	Rate of participants with mortality in intensive care unit	Through study completion, an average of 6 months
Secondary	In-hospital mortality	Number of participants with in-hospital mortality	Through study completion, an average of 6 months
Secondary	In-hospital mortality	Rate of participants with in-hospital mortality	Through study completion, an average of 6 months
Secondary	Mortality	Number of participants with all cause mortality	At 1, 3, and 6 months after CO poisoning
Secondary	Mortality	Rate of participants with all cause mortality	At 1, 3, and 6 months after CO poisoning
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Bradycardia	Number of participants with dropped heart rate indicated drug or interventions	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Secondary	Bradycardia	Rate of participants with dropped heart rate indicated drug or interventions	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Secondary	Hypokalemia	Number of participants with serum K concentration <3.0 - 2.5 mmol/L	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Secondary	Hypokalemia	Rate of participants with serum K concentration <3.0 - 2.5 mmol/L	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Secondary	Hyperkalemia	Number of participants with serum K concentration >6.0 - 7.0 mmol/L	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Secondary	Hyperkalemia	Rate of participants with serum K concentration >6.0 - 7.0 mmol/L	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Hypomagnesemia	Number of participants with serum magnesium <0.9 - 0.7 mg/dL	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Secondary	Hypomagnesemia	Rate of participants with serum magnesium <0.9 - 0.7 mg/dL	During the intervention (therapeutic hypothermia or normothermia) period (72 hours)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	S100ß (serum)	Concentration of S100ß (serum)	Within 14 days after CO exposure
Secondary	Neuronal specific enolase (serum)	Concentration of neuronal specific enolase (serum)	Within 14 days after CO exposure
Secondary	Brain magnetic resonance image (MRI)	Number of participants with brain injury in brain MRI	Within 14 days after CO exposure
Secondary	Brain magnetic resonance image (MRI)	Rate of participants with brain injury in brain MRI	Within 14 days after CO exposure