Clinical trial NCT05647707: The Efficacy of L-Carnitine in the Management of Acute Carbon Monoxide Poisoning
Official title: The Efficacy of L-Carnitine in the Management of Acute Carbon Monoxide Poisoning
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Carbon Monoxide Poisoning
Keywords: Carbon Monoxide Poisoning
Cardiotoxicity
Troponin
L-Carnitine
Outcome
Lead sponsor: Alexandria University
Sponsor class: OTHER
First posted: 2022-12-12
Enrollment: 72
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment randomized controlled clinical trial (phase II)
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Troponin level
timeFrame: In follow-up 24 hours after admission
Secondary outcomes:
measure: Duration of hospital stay
timeFrame: Assessed up to 1 month.
measure: The frequency of ICU admission
timeFrame: Assessed up to 1 month.
measure: Development of delayed neurological manifestations
timeFrame: Assessed up to 3 months following discharge from the hospital
Other outcomes:
Locations:
Study officials:
affiliation: Associate Professor of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
name: Zahraa K Sobh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor of Forensic Medicine and Clinical Toxicology. Head of department of Forensic Medicine and Clinical Toxicology. Chairperson of ethics committee Faculty of Medicine
name: Maha A Ghanem, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistant Lecturer of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
name: Heidi A Elsobky, MS
role: STUDY_DIRECTOR
affiliation: Demonstrator of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
name: Farah S Habib, Bachelor
role: STUDY_DIRECTOR
affiliation: Professor of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Tanta University, Alexandria, Egypt
name: Fatma Elgazzar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.