The Efficacy and Safety of Levetiracetam Versus Fosphenytoin in Convulsive Status Epilepticus: An Open Label Clinical Trial in Dhaka Medical College Hospital
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- To determine the efficacy and safety between Levetiracetam and Fosphenytoin in adult convulsive status epilepticus.
研究概览
简要总结
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.
详细描述
A randomized control trial will be conducted in the Department of Neurology, DMCH. Ethical approval will be obtained from the DMCH ethical review board before the study. After the selection of the subjects, the nature, purpose, and benefit of the study will be explained to each subject & their legal attendants in detail. They will be encouraged for voluntary participation. Informed written consent will be taken from the participants or their legal attendants. Diagnosis of Status epilepticus will be made according to the criteria of the ILAE task force on classification of status epilepticus (2015). The history of previous disease and habits as well as demographics, the type of SE, seizure duration before treatment, the cause of SE and family history will be recorded. In both groups, height and body weight were estimated from body habitus, family information, or patient records. Blood pressure will be measured. BMI will be calculated as weight (kg)height (m)2. In all patients, neurological assessment will be conducted routinely. Randomized sampling methods will be applied for selecting study subjects. Randomization will be carried out into two groups. After that group A will be treated with FHP and group B will be treated with LEV. Resuscitation and stabilization will be simultaneously performed to ensure airway patency, oxygen inhalation to prevent cerebral hypoxia, securing intravenous access & maintenance of blood pressure. Routine laboratory investigations (full blood count, blood glucose, electrolytes, calcium, magnesium, liver function test & renal function test) will be done. EEG will be done in all patients.
At first, Diazepam will be intravenously administered at 10 mg to all patients. Then, if SE (Status Epilepticus) is not controlled within 20 minutes from Diazepam needle time, study participants will be rapidly randomized and allocated to the FPHT and LEV groups.
In the FPHT group, FPHT 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.
In the LEV group, LEV 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.
Then, after 30 minutes following FPHT/LEV needle time reassessment of the patient will be done to determine the outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years
- •Patients with convulsive status epilepticus
- •Both male and female
- •Willing to give consent
排除标准
- •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
研究组 & 干预措施
Levetiracetam
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.
干预措施: Levetiracetam Injection (Drug)
Fosphenytoin
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.
干预措施: Fosphenytoin Injection (Drug)
结局指标
主要结局
To determine the efficacy and safety between Levetiracetam and Fosphenytoin in adult convulsive status epilepticus.
时间窗: At 24 hours
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.
次要结局
- Observe and compare the serious adverse event rate(At 30 minutes, at 24 hours and at Hospital discharge)
- Seizure cessation rate(Thirty minutes)
- 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)
- Seizure recurrence rate within 24 hours(24 hours)
- Modified Rankin Scale (mRS) score(At 30 minutes, at 24 hours and at Hospital discharge)
研究者
Dr. Reaz Mahmud
Assistant Professor
Dhaka Medical College