Efficacy, Safety, and Tolerability of Intramuscular Versus Intravenous Fosphenytoin for Pediatric Status Epilepticus - A Randomised-Controlled, Open-label, Non-inferiority Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 288
- 试验地点
- 1
- 主要终点
- Primary efficacy:
研究概览
简要总结
Primary research question?
Whether the efficacy, safety, and tolerability aspects of intramuscular fosphenytoin support its use as an adjunct abortive therapy in pediatric SE management when intravenous access is delayed or difficult, especially in primary-care or secondary-care settings?
Research hypothesis:
As an abortive therapy for pediatric SE, intramuscular fosphenytoin is non-inferior to intravenous fosphenytoin in achieving clinical and electrographic seizure cessation with better efficacy, safety, and tolerability profile.
What this study adds? How this study might affect research, practice, or policy:
·This study will compare efficacy, safety, and tolerability of intermuscular fosphenytoin in comparison with intravenous fosphenytoin in pediatric patients who will be admitting to emergency-triage due to out-hospital SE or to pediatric intensive-care due to in-hospital SE. It will provide ‘Class-I evidence’ about the choice of route of administration of fosphenytoin, especially when intravenous access is difficult or delayed.
·If the study demonstrates non-inferiority of intramuscular fosphenytoin when compared with intravenous fosphenytoin among pediatric patients with status epilepticus, it may change the clinical practice and potentially improve ease of treatment and reduce the cost of therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 2.00 Year(s) 至 6.00 Year(s)（—）
- 性别
- All
入选标准
- •Pediatric patients with age 2 months to 6 years, diagnosed with convulsive SE and who will be treated with consensually accepted cumulative dose of benzodiazepine (preferably midazolam nasal-spray), lasting or continue to have seizures for more than 5 minutes and no more than 30 minutes after the last dose of benzodiazepines.
- •The minimal adequate cumulative doses of benzodiazepines will be defined as diazepam at a dose of 0.3 mg per kilogram of body weight (administered intravenously or rectally), lorazepam at a dose of 0.1 mg per kilogram (administered intravenously), or midazolam at a dose of 0.3 mg of per kilogram (administered intramuscularly) or 0.2 mg per kilogram (administered intravenously or intranasally) for children who weighed less than 32 kg.
- •These drugs may have been administered in divided doses, including prior to patient’s arrival in the emergency department (out-hospital SE).
排除标准
- •The study will exclude patients who are already on antiseizure medication/s for the long-term control of seizure.
- •Those patients will also be randomly assigned to a treatment groups without regard to their antiseizure medication/s type.
- •Patients who arrive at the emergency department with one of the following conditions will be excluded from the study: patients with major head trauma as the acute precipitant of the seizure; cardiac arrest; or a hear rate less than 40 beats per minute (since these conditions require alternative treatments).
- •Patients who have priorly received treatment for their present episode of status epilepticus using antiseizure medications other than benzodiazepines or who have had their trachea intubated will be excluded from the study.
- •Patients with known allergy or contraindications to fosphenytoin, also the patients with comorbid conditions like known inborn metabolic disorder, cardiac arrhythmias, or severe renal impairment, will be excluded from the study.
结局指标
主要结局
Primary efficacy:
时间窗: Clinical seizure cessation at 30-minutes after administration of the study-drugs. Electrographic seizure cessation 2-hours after administration of loading dose of the study-drugs. | Improvement in the responsiveness at 60-minutes after the start of study-drugs. | Composite of life-threatening-hypotension or cardiac-arrhythmia within 60-minutes after the start of study-drug-infusion.
Proportion of patients with clinical seizure cessation at 30-minutes after administration of study-drugs, and electrographic seizure cessation at 2-hours after administration of loading-dose of the study-drugs. Improvement in the responsiveness at 60-minutes after the start of trial-drug, and no requirement of additional ASM.
时间窗: Clinical seizure cessation at 30-minutes after administration of the study-drugs. Electrographic seizure cessation 2-hours after administration of loading dose of the study-drugs. | Improvement in the responsiveness at 60-minutes after the start of study-drugs. | Composite of life-threatening-hypotension or cardiac-arrhythmia within 60-minutes after the start of study-drug-infusion.
Primary safety:
时间窗: Clinical seizure cessation at 30-minutes after administration of the study-drugs. Electrographic seizure cessation 2-hours after administration of loading dose of the study-drugs. | Improvement in the responsiveness at 60-minutes after the start of study-drugs. | Composite of life-threatening-hypotension or cardiac-arrhythmia within 60-minutes after the start of study-drug-infusion.
Composite of life-threatening-hypotension or cardiac-arrhythmia within 60-minutes after the start of study-drug-infusion.
时间窗: Clinical seizure cessation at 30-minutes after administration of the study-drugs. Electrographic seizure cessation 2-hours after administration of loading dose of the study-drugs. | Improvement in the responsiveness at 60-minutes after the start of study-drugs. | Composite of life-threatening-hypotension or cardiac-arrhythmia within 60-minutes after the start of study-drug-infusion.
次要结局
- Secondary efficacy outcome measure is the time required for seizure cessation or termination from the start of the study drug from either arm; admission to the intensive-care unit (ICU); length of ICU hospitalisation and overall hospital stay in days. The time interval between the start of the trial drug and cessation of the clinically apparent seizures will be referred as ‘time to seizure termination’.(Additional safety measures include endotracheal or tracheostomy intubation within 60 minutes, acute seizure recurrence between 60 minute to 12 hours, and acute anaphylaxis after the start of study drug infusion through IV or after the administration of IM injection.)
研究者
Dr Kavita Srivastava
Bharati Vidyapeeth Deemed University, Medical College and Hospital, Pune