The Efficacy and Safety of Levetiracetam Versus Fosphenytoin in Convulsive Status Epilepticus

NCT06403150 | Enrolling By Invitation Phase 4 DMC

• 1 other identifier: ERC-DMC/ECC/2023/131
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Status epilepticus (SE) is an emergency, life-threatening medical condition that may cause irreversible cerebral damage. Therefore, the rapid and secure cessation of seizures and resuscitation is crucial. Potent gamma-aminobutyric acid agonists, including benzodiazepines, are recommended as first-line treatments. For the complete cessation of SE and prevention of recurrence, long-acting antiepileptic drugs (e.g.- FPHT) are also required as second-line treatments along with short-acting benzodiazepines. Intravenous fosphenytoin (FPHT) is associated with fewer adverse events such as life-threatening arrhythmia, cardiac arrest, hypotension, and allergic reactions. Levetiracetam (LEV), is considered to be effective for SE with less serious adverse events including dizziness, somnolence, headache, and transient agitation, but there have been no reports of arrhythmias, hypotension, Stevens-Johnson syndrome, or hepatotoxicity. Preceding studies show that levetiracetam is similarly effective and associated with fewer adverse effects than those of fosphenytoin. Few trials have compared the effectiveness and safety of levetiracetam (LEV) and fosphenytoin (FHP) for status epilepticus worldwide. Moreover, genetic variation is likely to play a crucial role in the development of adverse drug reactions (ADRs) including drug resistance. By far, no study has yet been conducted addressing the issue of efficacy and safety between levetiracetam (LEV) and fosphenytoin (FHP) in status epilepticus in the context of the Bangladeshi population. A comparative study of the efficacy and safety of levetiracetam (LEV) and fosphenytoin (FHP) will be expected to give more confidence for the use of the drug. Considering this the study aims to assess the safety and efficacy of levetiracetam (LEV) and fosphenytoin (FHP) in status epilepticus. This study finding has an implication in the treatment protocol which will be beneficial for the patients and physicians as well. Furthermore, it will give input to the policymaker for developing new guidelines regarding status epilepticus management and also encourage future research.

Conditions

Status Epilepticus

Keywords

Status Epilepticus; Levetiracetam; Fosphenytoin

Outcome Measures

Primary Outcomes (1)

• To determine the efficacy and safety between Levetiracetam and Fosphenytoin in adult convulsive status epilepticus.

  The measurement of a medicine desire effect under ideal conditions, such as clinical trial ( European medicine agency). It is measured as percentage in reduction of seizure frequency from the time of drug initiation and also measure the Incidence of treatment-emergent adverse events.

  At 24 hours

Secondary Outcomes (6)

• Seizure cessation rate

  Thirty minutes

• Seizure recurrence rate within 24 hours

  24 hours

• Observe and compare the serious adverse event rate

  At 30 minutes, at 24 hours and at Hospital discharge

• Intubation rate within 24hours

  24 hours

• All-cause in-hospital mortality among patients

  From date of randomization until the date of death from any cause

Study Arms (2)

Levetiracetam

ACTIVE COMPARATOR

Levetiracetam at 60 mg/kg (max dose 4500 mg) will be intravenously administered in 100mL of normal saline at an administration rate of 2-5mg/kg/min or over 10 minutes.

Drug: Levetiracetam Injection

Fosphenytoin

ACTIVE COMPARATOR

Fosphenytoin at 20 mg/kg (Phenytoin equivalent dose of 15 mg/kg) will be intravenously administered in 100mL of normal saline at an administration rate not exceeding 3mg/kg/min or 150 mg/min.

Drug: Fosphenytoin Injection

Interventions

Levetiracetam Injection DRUG

Levetiracetam at 60 mg/kg (max dose 4500 mg) will be intravenously administered in 100mL of normal saline at an administration rate of 2-5mg/kg/min or over 10 minutes. After 30 minutes following Levetiracetam needle time reassessment of the patient will be done to determine the outcomes.

Also known as: Iracet Injection, Neurocet Injection

Levetiracetam

Fosphenytoin Injection DRUG

Fosphenytoin at 20 mg/kg (Phenytoin equivalent dose of 15 mg/kg) will be intravenously administered in 100mL of normal saline at an administration rate not exceeding 3mg/kg/min or 150 mg/min. After 30 minutes following the Fosphenytoin needle time reassessment of the patient will be done to determine the outcomes.

Also known as: Fosfen Injection

Fosphenytoin

Eligibility Criteria

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

You may qualify if:

• Age \>18 years
• Patients with convulsive status epilepticus
• Both male and female
• Willing to give consent

You may not qualify if:

• Patients with convulsive status epilepticus already intubated before treatment
• Acute precipitant of seizure was major trauma, hypoglycemia, hyperglycemia, cardiac arrest, or post-anoxia
• Known allergic to FPHT or LEV
• Pregnant patient
• Liver disease or severe renal impairment

Sponsors & Collaborators

• Dhaka Medical College: lead

Study Sites (1)

Dhaka Medical College Hospital

Dhaka, 1000, Bangladesh

Location

MeSH Terms

Conditions

Status Epilepticus

Interventions

Levetiracetam; fosphenytoin

Condition Hierarchy (Ancestors)

Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dr Md Amirul Islam, MBBS

  MD (Neurology) Phase B Resident

  PRINCIPAL INVESTIGATOR

• Professor Dr Kazi Gias Uddin Ahmed, MD

  Professor of Neurology, Dhaka Medical College

  STUDY CHAIR

• Dr Reaz Mahmud, MD

  Assistant Professor of Neurology, Dhaka Medical College

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 21, 2024
• First Posted: May 7, 2024
• Study Start: May 15, 2023
• Primary Completion: August 1, 2024
• Study Completion: October 1, 2024
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: May 2023 to October 2024
• Access Criteria: Those who works with Status Epilepticus patients

Locations

BA (1)