Acute PoisoningPhase 2NCT06316362
Efficacy of SMOF Lipid in the Management of Acute Poisoning With Carbamazepine
A Phase 2 study testing SMOF lipid 20% and Standard treatment for carbamazepine toxicity in people with Acute Poisoning, run by Alexandria University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 54 years
- Conditions the study is for
- Acute Poisoning
- What is being tested?
- SMOF lipid 20% and Standard treatment for carbamazepine toxicity
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jan 2022to 28 Feb 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 54 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- Patients will be excluded if they have 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 locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Conditions
- Acute Poisoning
- Being tested
- SMOF lipid 20%, Standard treatment for carbamazepine toxicity
- Keywords
- Carbamazepine poisoning, SMOF lipid, lipophilic agents
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SMOF lipid 20%Drug
SMOF 20%; a blend of (soybean oil, medium chain triglycerides, olive 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
Standard treatment for carbamazepine toxicityOther
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).
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
| Study group | Role | What they receive |
|---|---|---|
| control group | Other | The first group constitutes the control group that was administered the standard treatment protocol for carbamazepine toxicity. Receives: Other: Standard treatment for carbamazepine toxicity |
| SMOF lipid treated group | Active comparator | The second group received the SMOF lipid infusion in addition to the standard protocol. Receives: Drug: SMOF lipid 20% |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 carbamazepine 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, 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.
Measured: participants were monitored within 24 hours from admission to the hospital
Secondary outcomes (3)
Assessment of Intubation Requirement Using GCS and APACHE
This study investigates the requirement for intubation and mechanical ventilation among participants with acute carbamazepine 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.
Measured: 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 carbamazepine 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 carbamazepine poisoning.
Measured: 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
length of hospital stay
This study evaluates the length of stay in the hospital among participants with acute carbamazepine 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 carbamazepine poisoning.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2024
- Study start1 Jan 2022
- Primary completion1 Feb 2023
- Study completion28 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Acute PoisoningStudies of the same condition, open and under way.
- More trials run by Alexandria UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexandria University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Abeer Sheta, professor, Study chair, Alexandria University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06316362
- Sponsor's protocol ID
- SMOF in carbamazepine toxicity
- Status last verified
- Mar 2024
- First submitted
- 5 Mar 2024
- Last updated
- 10 Oct 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 27098056Karaman 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.
PubMed 29026556Jaffal 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.
PubMed 37242638Taftachi 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.
PubMed 22582483
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of SMOF Lipid in the Management of Acute Poisoning With Carbamazepine
- ClinicalTrials.gov ID
- NCT06316362
- Acronym / sponsor ID
- SMOF in carbamazepine toxicity
- Conditions
- Acute Poisoning
- Keywords
- Carbamazepine poisoning, SMOF lipid, lipophilic agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Alexandria UniversityUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 1 Feb 2023 (actual)
- Study completion
- 28 Feb 2023 (actual)
- First posted
- 18 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| control group | Other | Other: Standard treatment for carbamazepine toxicityThe first group constitutes the control group that was administered the standard treatment protocol for carbamazepine toxicity. |
| SMOF lipid treated group | Active comparator | Drug: SMOF lipid 20%The second group received the SMOF lipid infusion in addition to the standard protocol. |
Who may qualify
- Ages
- 18 to 54 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SMOF lipid 20%SMOF 20%; a blend of (soybean oil, medium chain triglycerides, olive 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 | Drug | SMOF lipid treated group |
| Standard treatment for carbamazepine toxicityHypotension 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). 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 | Other | control group |
Primary outcome
Improvement in Conscious Levels Measured by Glasgow Coma Scale (GCS)
Time frame: participants were monitored within 24 hours from admission to the hospital
This study evaluates the efficacy of SMOF lipid 20% in improving conscious levels among participants with acute carbamazepine 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, 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.
3 secondary outcomes
Assessment of Intubation Requirement Using GCS and APACHE
Time frame: participants were assessed within 24 hours from admission to the hospital
Length of Intensive Care Unit (ICU) Stay
Time frame: 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
length of hospital stay
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
- Background: PubMed 27098056Zyoud 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.
- Background: PubMed 29026556Karaman 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.
- Background: PubMed 37242638Jaffal 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.
- Background: PubMed 22582483Taftachi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abeer Sheta, professor study chair
Alexandria University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SMOF lipid 20% and Standard treatment for carbamazepine toxicity in people with Acute Poisoning, run by Alexandria University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in Conscious Levels Measured by Glasgow Coma Scale (GCS) (time frame: participants were monitored within 24 hours from admission to the hospital). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06316362, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2024.