Prevention of Epilepsy in Stroke Patients at High Risk of Developing Unprovoked Seizures: Anti-epileptogenic Effects of Eslicarbazepine Acetate
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 129
- 试验地点
- 22
- 主要终点
- Proportion of Patients Who Experience the First Unprovoked Seizures (US) Within the First 6 Months After Randomisation (Failure Rate)
研究概览
简要总结
This study aims to assess if eslicarbazepine acetate (ESL) treatment (started within 96 hours after stroke occurrence and continued for 30 days) changes the incidence of unprovoked seizures (USs) within the first 6 months after randomisation as compared to placebo
详细描述
This is a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial in patients with acute intracerebral haemorrhage with a Cortical involvement, Age <65 years, Volume of intracerebral haemorrhage > 10 ml and Early seizure within 7 days after intracerebral haemorrhage (CAVE) score ≥ 3 or an acute ischaemic stroke with a SeLECT score ≥ 6.
At the first visit (screening/baseline, V1a), patients will undergo several examinations to check eligibility. The next visit (V1b) has to be performed within 96 hours after primary stroke occurrence. After eligibility has been confirmed, patients will be randomised (randomisation ratio 1:1) to treatment with ESL 800 mg (Group A) or placebo (Group B).
Patients will start treatment with the investigational medicinal product (IMP), i.e. ESL or placebo, within 96 hours after primary stroke occurrence at V1b. They will continue treatment until Day 30 after randomisation and then be tapered off. Thereafter, patients will be followed up until 18 months after randomisation. Patients can concomitantly receive antiepileptic therapies, except commercially available ESL or oxcarbazepine, until Day 30.
Concomitant antiepileptic therapies have to be discontinued and down-titration has to be started according to the respective Summary of Product Characteristics (SmPC). If the antiepileptic drugs (AEDs)/benzodiazepine are not already discontinued before, downtitration must be started on Day 31 at the latest.
If one or more AS(s) occur(s) within 7 days after primary stroke, this will not result in change of IMP dose. Patients having a first US will discontinue IMP treatment and will be treated at the discretion of the investigator until 18 months after randomisation, except with commercially available ESL.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Patients must meet ALL of the following criteria:
- •Male or female patient aged 18 years or above;
- •Acute intracerebral haemorrhage with a CAVE score ≥ 3 or acute ischaemic stroke with a SeLECT score ≥ 6, in each case confirmed by magnetic resonance imaging (MRI)/computed tomography (CT).
- •Time of stroke occurrence is known and V1b is planned within 96 hours.
- •Brain scan analysis has reliably excluded structural brain lesions that can mimic stroke, e.g. cerebral tumour or brain abscess, etc.
- •a. Patient is able to give informed consent and to write and has signed written informed consent OR b. Patient is able to give informed consent, but unable to write and has provided verbal witnessed consent OR c. Patient is unable to give informed consent, but likely to regain this ability until V2, and the informed consent is deferred OR d. Patient is unable to give informed consent, but likely to regain this ability until V2, and patient's legal representative (according to the respective national/local requirements) has provided written informed consent.
- •Female patients without childbearing potential (2 years postmenopausal, bilateral oophorectomy or tubal ligation, or complete hysterectomy) are eligible. Female patients with childbearing potential must not be pregnant as confirmed by a negative pregnancy test and sexually active females must use a medically acceptable effective nonhormonal method of contraception up to the end of the current menstrual cycle after stopping treatment. Acceptable methods for women are surgical intervention (e.g. bilateral tubal occlusion), intrauterine device, double-barrier methods, true sexual abstinence (i.e. when this is in line with the preferred and usual lifestyle of the patient) and vasectomised male partner, provided that he is the sole partner of that patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- •Inclusion criteria at V1b
- •V1b is within 96 hours after stroke occurrence. Inclusion criteria at V2 (only applicable for patients who were unable to give informed consent at V1a.)
- •a. Patient is able to give informed consent and to write and has signed a written informed consent OR b. Patient is able to give informed consent, but unable to write and has provided verbal witnessed consent.
排除标准
- •Patients are to be excluded from the trial for ANY ONE of the following reasons:
- •Contraindication to ESL, i.e. known hypersensitivity to ingredients of ESL formulation or other carboxamide derivatives (e.g., oxcarbazepine, carbamazepine), or second or third degree atrioventricular (AV) block not corrected with a permanent pacemaker.
- •Known Han Chinese or Thai ancestry.
- •History of previous stroke (other than the one described in inclusion criteria no. 2 - 3).
- •Sinus venous thrombosis.
- •Spontaneous sub-arachnoid haemorrhage due to e.g. aneurysmatic or arteriovenous malformation.
- •History of USs prior to primary stroke.
- •Impaired pre-stroke level of function, i.e. modified Rankin Scale (mRS) score > 3 prior to first stroke occurrence.
- •History of AED use before primary stroke within the last 5 years as defined in the list of not allowed AEDs.
- •Use of ESL, unless provided as IMP of this trial, and oxcarbazepine.
- •Severe hepatic impairment.
- •Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (measured at V1a).
- •Known or suspected acute or chronic alcoholism, delirium tremens, or toxic psychosis.
- •History of suicidal ideation or suicide attempt within the past 3 years.
- •Presence of any other significant or progressive/unstable medical condition that, in the opinion of the investigator, would compromise evaluation of the trial treatment or may jeopardise the patient's safety, compliance or adherence to protocol requirements, such as significant psychiatric, cardiovascular, respiratory, metabolic, endocrine, haematologic, infectious or neurological disease.
- •For women: Pregnancy or breast-feeding.
- •Previous enrolment in this trial or participation in any other investigational drug trial within the past 30 days (or 5 half-lives of IMP whichever is longer) prior to V1a.
- •Persons committed to an institution by virtue of an order issued either by the judicial or other authorities.
- •Employees of the investigator or trial centre, with direct involvement in the proposed trial or other studies under the direction of that investigator or trial centre, as well as family members of the employees or the investigator.
研究组 & 干预措施
Group A
ESL 800 mg
干预措施: ESL 800 mg (Drug)
Group B
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of Patients Who Experience the First Unprovoked Seizures (US) Within the First 6 Months After Randomisation (Failure Rate)
时间窗: First 6 months after randomisation
Deaths before the first US or patients without evaluable assessment of the primary endpoint will be counted as treatment failures. To show that ESL (Group A) is superior to placebo (Group B), the primary null hypothesis will be tested against the alternative hypothesis
次要结局
- Number of Acute Symptomatic Seizure (ASS)(During the first 7 days after stroke)
- Proportion of Patients Who Experience the First US During the First 12 Months After Randomisation(First 12 months after randomisation)
- Proportion of Patients Who Experience the First US During the Course of the Trial(Until 18 months after randomisation)
- Probability of Failure at 6, 12, and 18 Months After Randomization(Over 18 months follow-up period)
- Time to First US After Stroke Occurrence.(Over 18 months follow-up period)
- Number and 4-week Rate of USs (4-week Rate of USs Was Omitted With SAP, Final Version 1.0, 22 NOV 2023).(Over 18 months follow-up period)
- Barthel Index (BI) Original 10-item Version(Barthel Index data is collected at Baseline, V3 (+37 days), V5 (+26 weeks), V7 (+52 weeks), End of trial visit (EOT, +78 weeks) or Early discontinuation visit (EDV, on average 30 days), and Endpoint (18 months).)
- National Institutes of Health Stroke Scale (NIHSS)(National Institutes of Health Stroke Scale (NIHSS) data is collected at Baseline, V3 (+37 days), V5 (+26 weeks), V7 (+52 weeks), End of trial visit (EOT, +78 weeks) or Early discontinuation visit (EDV, on average 30 days), and Endpoint (18 months).)
- Patient Health Questionnaire (PHQ-9)(Over 18 months follow-up period)
- Overall Survival at 6, 12, and 18 Months After Randomization(Over 18 months follow-up period)
- Treatment Emergent Adverse Events (TEAEs) Incl. Findings From Physical and Neurological Examinations(Over 18 months follow-up period)
- Clinically Significant Haematology Abnormalities(Over 18 months follow-up period)
- Clinically Significant Biochemistry Abnormalities, Including eGFR (Estimated Glomerular Filtration Rate) and Coagulation(Over 18 months follow-up period)
- Clinically Significant Urinalysis Abnormalities(Over 18 months follow-up period)
- Clinically Significant Vital Sign Abnormalities: Blood Pressure(Over 18 months follow-up period)
- Clinically Significant Vital Sign Abnormalities: Heart Rate(Over 18 months follow-up period)
- Electrocardiogram (ECG)(A standard 12-lead electrocardiogram (ECG) is performed at Baseline, V2 (+7 days), V3 (+37 days), Early discontinuation visit (if EDV performed before V3, on average 30 days).)
- Suicidal Ideation and Behaviour, Assessed by PHQ-9 (Question 9)(The PHQ-9 will be collected at Baseline, V3 (+37 Days), V5 (+26 weeks), V7 (+52 weeks), End of trial visit (EOT, +78 weeks) or Early discontinuation visit (if EDV performed before V3, on average 30 days), and Endpoint (18 months).)
- Number of Participants With and Without Seizures Based on Electroencephalogram (EEG)(Two recordings were provided: one carried out before in the initial phase of enrollment into the trial at V1a (< 96 hours) and the second one after termination of eslicarpazepine acetate intake (EOT, +78 weeks).)