Clinical trial NCT06316362: Efficacy of SMOF Lipid in the Management of Acute Poisoning With Carbamazepine
Official title: Efficacy of SMOF Lipid in the Management of Acute Poisoning With Carbamazepine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Poisoning
Keywords: Carbamazepine poisoning
SMOF lipid
lipophilic agents
Lead sponsor: Alexandria University
Sponsor class: OTHER
First posted: 2024-03-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of the current study was to evaluate whether SMOF lipid administration could be used as an adjuvant therapy to treat acute, moderate-to-severe carbamazepine poisoning.

Detailed description: Among anticonvulsants, carbamazepine (CBZ) is considered one of the most commonly reported poisonings. Carbamazepine (CBZ) was approved for use as a primary anticonvulsant agent following its initial use for trigeminal neuralgia. Further indications for the drug included treatment for bipolar disorder, resistant schizophrenia, and pain syndromes.

The wide availability of carbamazepine increases the potential for overdose, either accidentally or intentionally. The American Association of Poison Control Centres reported 2,562 hazardous exposures to CBZ in 2020. In addition, CBZ was the most commonly used anti-epileptic drug, according to a recent study by the National Centre for Environmental and Clinical Toxicology Research, Cairo, Egypt.

CBZ works by blocking presynaptic voltage-gated sodium channels, thereby inhibiting the release of synaptic glutamate and other neurotransmitters.

Overdose of CBZ is clinically manifested by nystagmus, nausea, dysarthria, ataxia, sedation, delirium, mydriasis, ophthalmoplegia, and myoclonus. The serious clinical problems resulting from large overdoses of CBZ are cardiotoxicity, respiratory depression, apnea, seizures, and coma. Mortality from CBZ poisoning is uncommon.

Because there is no definitive antidote for carbamazepine poisoning, poison control centres recommend supportive therapy based on the patient's clinical condition and multiple-dose activated charcoal (MDAC) as a specific intervention for enhanced elimination. Nevertheless, the elimination of the drug from the body can be prolonged.

The scarcity of physiological antidotes for acute poisonings encourages toxicologists to supplement standard supportive treatment protocols with promising agents that tend to improve morbidity and mortality.

In this context, intravenous lipid emulsions (ILE) are mainly used as a source of energy and essential fatty acids in patients requiring parenteral nutrition. Apart from their nutritional value, lipid emulsion therapy is becoming increasingly popular in critical care settings as a treatment for toxicity with lipophilic agents, particularly when the standard remedies are ineffective.

Following the encouraging outcomes of using ILEs for the treatment of local anaesthetic systemic toxicity, subsequent studies reported the therapeutic effect of ILEs in acute poisonings with other xenobiotics. However, the evidence for the potential effectiveness of ILE in clinical toxicology consists mainly of case reports and experimental studies. In cases of CBZ poisoning, ILE was not evaluated using a randomised control trial (RCT).

ILE may be suitable for the treatment of CBZ toxicity due to its lipid solubility. To the best of our knowledge, the effect of ILE therapy on acute carbamazepine poisoning has not been studied sufficiently.

SMOF 20%, a blend of soybean oil, medium-chain triglycerides, olive oil, and fish oil, is a new lipid emulsion product that has shown better therapeutic results regarding parentral nutrition when compared with traditional ones such as Intralipid® 20%. It has been associated with decreased oxidative injury, improved liver function, and increased antioxidant activity

Eligibility criteria: Inclusion Criteria:

The patients were enrolled in the study in accordance with the following:

1. Gender and age: adult symptomatic males and females.
2. Patients were admitted within 12 hours of exposure to the poison.
3. Patients received no prior treatment before admission.
4. Patients with moderate-to-severe carbamazepine poisoning according to the Poisoning Severity Score (PSS)
5. Patients classified as high-risk (HR) with anti-depressant overdose risk assessment (ADORA) criteria.

Exclusion Criteria:

Patients will be excluded if they have any of the following conditions:

1. pregnant and lactating women.
2. Patients with major medical conditions (e.g. diabetes mellitus), cardiovascular disease, renal, or hepatic failure).
3. Patients suffering from hyperlipidemia.
4. Malignancy.
5. Co-ingestion.

Primary outcomes:
measure: Improvement in Conscious Levels Measured by Glasgow Coma Scale (GCS)
timeFrame: participants were monitored within 24 hours from admission to the hospital
Secondary outcomes:
measure: Assessment of Intubation Requirement Using GCS and APACHE
timeFrame: participants were assessed within 24 hours from admission to the hospital
measure: Length of Intensive Care Unit (ICU) Stay
timeFrame: Participants will be monitored throughout their hospitalisation period, and the length of their ICU stay will be recorded from date of randomization until the date of last documented progression up to one month
measure: length of hospital stay
timeFrame: Participants will be monitored throughout their hospitalisation period, and the length of their hospital stay will be recorded from date of randomization until the date of last documented progression up to one month
Other outcomes:
Locations:
city: Alexandria
country: Egypt
facility: Faculty of Medicine
Study officials:
affiliation: Alexandria University
name: Abeer Sheta, professor
role: STUDY_CHAIR
References:
citation: Zyoud SH, Waring WS, Al-Jabi SW, Sweileh WM, Rahhal B, Awang R. Intravenous Lipid Emulsion as an Antidote for the Treatment of Acute Poisoning: A Bibliometric Analysis of Human and Animal Studies. Basic Clin Pharmacol Toxicol. 2016 Nov;119(5):512-519. doi: 10.1111/bcpt.12609. Epub 2016 May 20.
citation: Karaman K, Turkdogan KA, Deniz AT, Canakci SE. Which is the best in carbamazepine overdose? Clin Case Rep. 2017 Aug 22;5(10):1612-1615. doi: 10.1002/ccr3.1118. eCollection 2017 Oct.
citation: Jaffal K, Chevillard L, Megarbane B. Lipid Emulsion to Treat Acute Poisonings: Mechanisms of Action, Indications, and Controversies. Pharmaceutics. 2023 May 3;15(5):1396. doi: 10.3390/pharmaceutics15051396.
citation: Taftachi F, Sanaei-Zadeh H, Sepehrian B, Zamani N. Lipid emulsion improves Glasgow coma scale and decreases blood glucose level in the setting of acute non-local anesthetic drug poisoning--a randomized controlled trial. Eur Rev Med Pharmacol Sci. 2012 Mar;16 Suppl 1:38-42.