The Efficacy of L-Carnitine in the Management of Acute Carbon Monoxide Poisoning

Study Overview
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Brief Summary
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Carbon monoxide (CO) poisoning results in high morbidity and mortality worldwide. CO is described as a silent killer because CO is colorless, odorless, and tasteless but highly toxic. The diagnosis of acute CO poisoning depends on the history of exposure to a source of fire in a closed space along with the clinical and laboratory findings. The pathophysiology of CO poisoning is not fully understood; however, it is proved that CO induces hypoxia by forming carboxyhemoglobin (COHb) and shifting the oxygen dissociation curve to the left. The molecular mechanisms of CO poisoning include oxidative injury through the generation of free radicals. In addition, oxygen therapy might enhance the reactive oxygen species (ROS) production and result in reperfusion injury. Free radicals could induce a serious impact on vital organs, including the heart, and brain. L-Carnitine is an endogenous mitochondrial constituent that contributes to normal mitochondrial activities. L-Carnitine is an antioxidant with potent ROS scavenging ability. ROS-mediated pathology of CO suggests that antioxidants are potentially useful agents in the alleviation of CO toxicity. Thus, the current study will investigate the therapeutic efficacy of L-Carnitine in improving the prognosis of acute CO poisoning. The current clinical trial will include patients with moderate and severe acute carbon monoxide poisoning according to Poisoning Severity Score.

Detailed Description
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A randomized clinical trial (phase II) will be conducted at Alexandria Main University Hospital. The total required sample size is 72. The sample size was calculated by G power 3.1.9.4 software program depending on the primary outcome. According to these assumptions: Effect size, defined as the difference between group 1 and group 2 in the mean troponin levels at 24 hr, was calculated according to Sun et al. (2011) and was 0.657, alpha error =0.05, power of 80%, allocation ratio 1:1. A 20% expected attrition was added to the sample size to account for loss to follow-up. So, the final sample size was 72; 36 patients per group. All patients will be subject to the following: History taking: Personal data: age, and sex. Exposure-related data: circumstances of exposure, and time till hospitalization. Past medical history. Clinical assessment: Glasgow coma scale, vital signs, and general examination. Laboratory investigations: arterial blood gases (ABG), Carboxy hemoglobin level (COHb), and cardiac enzymes (CPK, CK-MB, Troponin). Electrocardiogram (ECG).

Official Title
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The Efficacy of L-Carnitine in the Management of Acute Carbon Monoxide Poisoning

Conditions
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Carbon Monoxide Poisoning

Intervention / Treatment
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* Dietary Supplement: L-Carnitine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The current clinical trials will include patients with moderate and severe acute carbon monoxide poisoning according to Poisoning Severity Score. Exclusion Criteria: When the diagnosis of acute carbon monoxide poisoning is unconfirmed. Patients with advanced cardiac and neurological diseases.
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
Interventional Model Description: Parallel Assignment randomized controlled clinical trial (phase II)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional Group<br>This group will comprise 36 patients who will receive conventional supportive treatment for the management of acute CO poisoning that include the following: Airway: maintaining clear patent airways. Breathing: High-flow normobaric oxygen (NBO) Hyperbaric oxygen (HBO) (if indicated). Mechanical ventilation ( if required). Circulation: intravenous fluids, and treatment of arrhythmias according to ECG abnormalities. | |
| Experimental: L-Carnitine Group<br>The 36 patients will receive conventional supportive care as in the conventional group in addition to IV L-carnitine. | Dietary Supplement: L-Carnitine<br>* The 36 patients will receive conventional supportive care in addition to IV L-carnitine with a loading dose of 100 mg/kg IV over 30-60 min (maximum 6 g) and the maintenance dose of 50 mg/kg IV every 8 h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Troponin level | Measure Troponin level in blood samples of patients | In follow-up 24 hours after admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of hospital stay | Time passed from the date of admission to the documented date of discharge or death, whichever came first | Assessed up to 1 month. | 
| The frequency of ICU admission | The number of patients admitted to ICU from the time of admission till the documented date of discharge or death, whichever came first. Patients who developed serious cardiovascular or neurological manifestations or need mechanical ventilation are indicated for ICU admission. | Assessed up to 1 month. | 
| Development of delayed neurological manifestations | The number of patients who developed impaired memory and or concentration. | Assessed up to 3 months following discharge from the hospital | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carbon Monoxide Poisoning, Cardiotoxicity, Troponin, L-Carnitine, Outcome