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Efficacy of SMOF Lipid in the Management of Acute Poisoning With Clozapine

A

Alexandria University

Status and phase

Completed
Phase 2

Conditions

Acute Poisoning

Treatments

Other: standard treatment for clozapine toxicity
Other: SMOF lipid 20%

Study type

Interventional

Funder types

Other

Identifiers

NCT06413589
SMOF in clozapine toxicity

Details and patient eligibility

About

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 clozapine poisoning.

Full description

Antipsychotics, a class of drugs primarily used to treat schizophrenia and various mood disorders, including bipolar disorder, encompass a medication like clozapine. Clozapine stands out among antipsychotics due to its lower incidence of extrapyramidal symptoms, such as tardive dyskinesia, and its effectiveness in addressing negative symptoms of schizophrenia.

Recent data from the American Association of Poison Control Centers (AAPCC) highlight sedatives/hypnotics/antipsychotics as among the top five frequently encountered xenobiotics in human exposure cases. This class of drugs has seen a notable uptick in incidence over the past 18 years. In Egypt, studies from institutions like Tanta University Poison Control Centre (TUPCC) and the National Poisoning Center in Cairo have identified acute clozapine poisoning as a common occurrence within cases of pharmaceutical drug poisonings affecting the central nervous system.

Clozapine toxicity manifests across multiple organ systems, with the central nervous system (CNS) and cardiovascular system (CVS) being most significantly impacted. Common symptoms include pronounced sedation, confusion, delirium, tachycardia, and mild hypotension.

Because there is no definitive antidote for clozapine 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.

ILE may be suitable for the treatment of clozapine toxicity due to its lipid solubility.

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

Enrollment

40 patients

Sex

All

Ages

18 to 66 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

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

Exclusion criteria

Patients were excluded if they had any of the following conditions:

pregnant and lactating women. Patients with major medical conditions (e.g. diabetes mellitus), cardiovascular disease, renal, or hepatic failure).

Patients suffering from hyperlipidemia. Malignancy. Co-ingestion.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

40 participants in 2 patient groups

control group
Other group
Description:
The first group constitutes the control group that was administered the standard treatment protocol for clozapine toxicity.
Treatment:
Other: standard treatment for clozapine toxicity
SMOF lipid treated group
Active Comparator group
Description:
The second group received the SMOF lipid infusion in addition to the standard protocol.Drug: SMOF lipid 20% SMOF 20%; a blend of soybean oil, medium-chain triglycerides, olive oil, and fish oil, is a new lipid emulsion product that was provided as a bolus dose of 1.5ml/kg for one hour, followed by a maintenance dose of 6 ml/kg for a period of four hours to the active comparator group
Treatment:
Other: SMOF lipid 20%

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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