A Multicentre, Double-blind, Randomized, Phase IV Clinical Trial Comparing the Safety, Tolerability and Efficacy of Levetiracetam Versus Lamotrigine and Carbamazepine in the Oral Antiepileptic Therapy of Newly Diagnosed Elderly Patients With Focal Epilepsy.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 361
- 试验地点
- 1
- 主要终点
- 58-week Retention Rate Measured by the Number of Drop Outs Due to Adverse Events or Seizures From Day 1 of Treatment
研究概览
简要总结
In this clinical trial patients with newly diagnosed focal epilepsy aged 60 years or older receive three different antiepileptic drugs in a double-blind, randomized design over a period of 58 weeks. All drugs are licensed for the treatment of epilepsy. The primary endpoint of this study will be retention rate at 58-weeks, since it reflects both efficacy and tolerability.
详细描述
Indication: Focal Epilepsy Objectives: To evaluate the tolerability and efficacy of levetiracetam (LEV) in newly diagnosed elderly patients (aged 60 yrs or above) with focal epilepsy compared to lamotrigine (LTG) or carbamazepine slow release (CBZ).
Primary Outcome: The primary outcome will be the 58-week retention rate measured by the number of drop outs due to adverse events or seizures from day 1 of treatment.
Secondary Outcome: Proportion of patients remaining seizure-free at week 30 (Visit 4); proportion of patients remaining seizure free at week 58 (Visit 6); the time (in days) to first break-through seizure (from day 1 of treatment); the absolute seizure frequency during the maintenance (over 52 weeks) phase; proportion of seizure-free days during the maintenance phase for subjects who enter the maintenance phase; the frequency of adverse events (from day 1 of treatment); QOLIE-31 results at V6; Portland Neurotoxicity scale at V6; results of cognitive testing (EpiTrack© by UCB).
Trial Design: This is a randomized, double-blind, multicenter Phase IV study using a parallel group design with three treatment groups. The study will consist of a 6-week titration-phase and a 52-week maintenance phase. Patients who successfully complete the trial (final visit, V6) will be unblinded and offered either to continue on their current drug or be changed to an alternative antiepileptic drug (AED) treatment of choice.
Population: Patients aged 60 years or above with new onset focal epilepsy i.e. either at least one epileptic seizure in the last 6 months and focal epileptiform discharges on EEG or a relevant lesion on CT/MRI or a total of 2 epileptic seizures, one of which occurring in the last 6 months prior inclusion. Patients with acute (< 2 weeks) symptomatic epileptic seizures due to acute brain abnormalities (i.e. haemorrhage or cerebral infarct), or contraindications against any of the drugs in trial will be excluded.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 60 yrs or above.
- •New onset focal epilepsy i.e. either at least one epileptic seizure in the last 6 months and focal epileptiform discharges on EEG or a relevant lesion on CT/MRI or at least 2 epileptic seizures, one of which occurring in the last 6 months prior inclusion.
- •No previous AED treatment, except for a period not longer than 4 weeks prior to inclusion (V0).
- •Ability of subject to understand verbal and written instructions, to comply with all study requirements, and to comprehend character and individual consequences of the clinical trial.
- •Written informed consent before enrolment in the trial.
排除标准
- •Acute symptomatic epileptic seizures occurring acutely within a 2 week period after the onset of an acute illness such as cerebral haemorrhage, cerebral infarct, rapid progressive malignancy or other acute brain abnormalities (i.e. encephalitis, hypoxic brain damage, trauma, metabolic derangement, following brain surgery).
- •Dementia (as defined by history)
- •Renal insufficiency as defined by GFR < 50 mL/min.
- •Increased liver enzymes (GOT, GPT, gGT) or increased bilirubin ≥ 2-fold the upper limit of normal (ULN).
- •Pre-treatment with valproic acid within the four weeks prior inclusion (V0).
- •Contraindication against or history of hypersensitivity to any of the investigational medicinal products or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal products.
- •Participation in other clinical trials and observation period of competing trials within the last 2 months, respectively.
- •History of drug or alcohol abuse within the last 2 years.
- •Medical condition which interferes with the participation in the trial according to the opinion of the investigator.
- •Patients with life expectancy < 1 year due to malignant disease
- •Psychiatric morbidity requiring legal guardianship.
研究组 & 干预措施
Levetiracetam
Levetiracetam
干预措施: Levetiracetam (Drug)
Carbamazepine
Carbamazepine
干预措施: Carbamazepine (Drug)
Lamotrigine
Lamotrigine
干预措施: Lamotrigine (Drug)
结局指标
主要结局
58-week Retention Rate Measured by the Number of Drop Outs Due to Adverse Events or Seizures From Day 1 of Treatment
时间窗: 58 weeks
次要结局
- Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4)(Week 30)
- Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6)(week 58)
- The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment)(over the whole duration of 58 weeks)
- The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58)(over 52 weeks)
- Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase(52 weeks)
- QOLIE-31 (Quality Of Life In Epilepsy) Results at V6(58 weeks, final visit)
- Portland Neurotoxicity Scale (PNS) at V6(at week 58)
- Time to Drop Out(58 weeks)
- Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6(week 58)
- Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6(58 weeks)
- Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6)(week 58)
研究者
Konrad J. Werhahn
Prof of Neurology, Head Section on Epilepsy
Johannes Gutenberg University Mainz