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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Carbon Monoxide Poisoning
• Intervention / Treatment: Dietary supplement: L-Carnitine

Detailed Description

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:

1. History taking:

   • Personal data: age, and sex.
   • Exposure-related data: circumstances of exposure, and time till hospitalization.
   • Past medical history.

2. 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).

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zahraa K Sobh, MD; Phone Number: +2 01020744739; Email: zahraa.sobh@alexmed.edu.eg
• Study Contact Backup: Name: Maha A Ghanem, MD; Phone Number: +2 01223374415; Email: ghanemmaha63@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Conventional Group; 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; The 36 patients will receive conventional supportive care as in the conventional group in addition to IV L-carnitine.	Dietary supplement: L-Carnitine; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexandria University
• Investigators: Principal Investigator: Zahraa K Sobh, MD, Associate Professor of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; Principal Investigator: Maha A Ghanem, MD, Professor of Forensic Medicine and Clinical Toxicology. Head of department of Forensic Medicine and Clinical Toxicology. Chairperson of ethics committee Faculty of Medicine; Study Director: Heidi A Elsobky, MS, Assistant Lecturer of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; Study Director: Farah S Habib, Bachelor, Demonstrator of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; Principal Investigator: Fatma Elgazzar, MD, Professor of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Tanta University, Alexandria, Egypt

Publications and helpful links

General Publications

• Sherif NA, El-Banna AS, ElBourini MM, Khalil NO. Efficacy of L-carnitine and propranolol in the management of acute theophylline toxicity. Toxicol Res (Camb). 2020 Mar 11;9(1):45-54. doi: 10.1093/toxres/tfaa002. eCollection 2020 Feb.
• Elgazzar FM, Elgohary MS, Basiouny SM, Lashin HI. Intravenous lipid emulsion as an adjuvant therapy of acute clozapine poisoning. Hum Exp Toxicol. 2021 Jul;40(7):1053-1063. doi: 10.1177/0960327120983873. Epub 2021 Jan 5.
• Sun ZJ, Yang CB, Wang H, Li Y. [The impact of L-carnitine administration on the serum level of myocardium injury markers in patients with acute carbon monoxide poisoning]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2011 Dec;23(12):739-42. Chinese.
• Zengin S, A B, Karta S, Can B, Orkmez M, Taskin A, Lok U, Gulen B, Yildirim C, Taysi S. An assessment of antioxidant status in patients with carbon monoxide poisoning. World J Emerg Med. 2014;5(2):91-5. doi: 10.5847/wjem.j.issn.1920-8642.2014.02.002.
• Yildiz MN, Eroglu SE, Ozen C, Yildiz HA, Sektioglu BK, Alkan C. Analysis of the effects of COHb, lactate, and troponin levels on the clinical process and outcome in patients who were admitted to the emergency service due to carbon monoxide poisoning. North Clin Istanb. 2019 May 29;6(2):141-145. doi: 10.14744/nci.2018.88709. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 15, 2022
• Primary Completion (Anticipated): April 15, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: November 27, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Estimate): December 12, 2022

Study Record Updates

• Last Update Posted (Estimate): December 12, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Cardiotoxicity; Outcome; L-Carnitine; Troponin; Carbon Monoxide Poisoning
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Gas Poisoning; Poisoning; Carbon Monoxide Poisoning
• Other Study ID Numbers: 0304888

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: The confidentiality of the personal data of participants will be maintained. The current study will be published in an academic journal, then, the published data could be accessed and used for any purpose.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No