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

NCT06413589 | Completed Phase 2

• 1 other identifier: SMOF in clozapine toxicity
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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 clozapine poisoning.

Conditions

Acute Poisoning

Keywords

clozapine poisoning; SMOF lipid; lipophilic agents

Outcome Measures

Primary Outcomes (4)

• Improvement in Conscious Levels Measured by Glasgow Coma Scale (GCS)

  This study evaluates the efficacy of SMOF lipid 20% in improving conscious levels among participants with acute clozapine poisoning within 24 hours. Conscious level improvement is assessed using the Glasgow Coma Scale (GCS), a widely recognised tool for neurological assessment. The GCS measures eye opening, verbal response, and motor response. The minimum value is 3 and the maximum value is 15, with higher scores indicating better conscious levels. The study aims to determine the extent of improvement in GCS scores following SMOF lipid administration, providing valuable insights into its effectiveness in enhancing neurological function.

  participants were monitored within 24 hours from admission to the hospital

• Assessment of Intubation Requirement Using APACHE

  This study investigates the requirement for intubation and mechanical ventilation among participants with acute clozapine poisoning using multiple clinical assessment tools, including the Glasgow Coma Scale (GCS) and Acute Physiology and Chronic Health Evaluation (APACHE). The GCS evaluates the level of consciousness based on eye opening, verbal response, and motor response, with lower scores indicating a higher likelihood of intubation and mechanical ventilation. The APACHE score assesses the severity of illness and predicts the need for respiratory support, with higher scores indicating an increased risk of respiratory failure and the requirement for intervention.

  participants were assessed within 24 hours from admission to the hospital

• Length of Intensive Care Unit (ICU) Stay

  This study evaluates the length of stay in the Intensive Care Unit (ICU) among participants with acute clozapine poisoning. The length of the ICU stay is defined as the duration from the time of admission to the ICU to discharge from the ICU in days. Participants will be monitored throughout their hospitalisation period, and the length of their ICU stay will be recorded. The study aims to assess the impact of SMOF lipid administration on the duration of ICU stays, providing insights into its effectiveness in optimising resource utilisation and patient management. Understanding the factors influencing the length of the ICU stay may contribute to improved healthcare delivery and patient outcomes in acute clozapine poisoning.

  up to one month

• length of hospital stay

  This study evaluates the length of stay in the hospital among participants with acute clozapine poisoning. The length of stay is defined as the duration from the time of admission to the hospital to discharge from the hospital in days. Participants will be monitored throughout their hospitalisation period, and the length of their hospital stay will be recorded. The study aims to assess the impact of SMOF lipid administration on the duration of hospital stays, providing insights into its effectiveness in optimising resource utilisation and patient management. Understanding the factors influencing length of stay may contribute to improved healthcare delivery and patient outcomes in acute clozapine poisoning.

  up to one month

Study Arms (2)

control group

OTHER

The first group constitutes the control group that was administered the standard treatment protocol for clozapine toxicity.

Other: standard treatment for clozapine toxicity

SMOF lipid treated group

ACTIVE COMPARATOR

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

Other: SMOF lipid 20%

Interventions

SMOF lipid 20% OTHER

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

SMOF lipid treated group

standard treatment for clozapine toxicity OTHER

Hypotension was initially treated with isotonic crystalloid; vasopressors were utilised if intravenous fluids failed to restore the hypotension. This was in the form of norepinephrine with a dose of 0.05 μg/kg/min and titrated till reaching the goal mean arterial pressure (\>65 mmHg) \[29\]. Those experiencing seizures due to CBZ overdose were treated with benzodiazepines (diazepam) at a dose of 10-20 mg. Benzodiazepines are considered allosteric modulators of the gamma-aminobutyric acid channel. MDAC (50 grammes every six hours) was given to all patients in the current study. Those with severe poisoning were given the MDAC after securing the airway with a cuffed endotracheal tube

control group

Eligibility Criteria

• Age: 18 Years - 66 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexandria University: lead

Study Sites (1)

Faculty of Medicine

Alexandria, Egypt

Location

Related Publications (4)

• 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.

  PMID: 37242638 BACKGROUND

• 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.

  PMID: 33401984 BACKGROUND

• 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.

  PMID: 22582483 BACKGROUND

• Ok SH, Sohn JT. Effect of lipid emulsion on acute clozapine poisoning-induced QT prolongation. Hum Exp Toxicol. 2021 Dec;40(12):2237-2239. doi: 10.1177/09603271211025598. Epub 2021 Jun 17. No abstract available.

  PMID: 34137281 BACKGROUND

Study Officials

• Abeer Sheta, professor

  Alexandria University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: May 14, 2024
• Study Start: January 1, 2022
• Primary Completion: February 1, 2023
• Study Completion: February 28, 2023
• Last Updated: May 14, 2024

Record last verified: 2024-04

Locations

EG (1)