An Open Randomized Trial to Assess the Efficacy and Safety of Vagus Nerve Stimulation (VNS) Versus New Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 134
- 试验地点
- 19
- 主要终点
- Proportion of Responders After 1 Year of Follow-up (ITT-population)
研究概览
简要总结
This is a randomized study designed to compare long-term treatment outcomes in pediatric patients with refractory seizures treated with VNS (Vagus Nerve Stimulation) Therapy versus anti-epileptic drugs (AEDs). Seizure reduction, quality of life measures, and side effect profiles will be evaluated. The results of this study will provide controlled comparative data to better guide physicians in determining the best overall treatment strategy for patients with seizures who have failed initial AED therapy.
详细描述
This was a randomized, parallel group, multi-center study. Screening Visit (visit 1) Subjects, parents, and the investigator signed and dated the informed consent after which subject eligibility was checked. Eligible subjects were entered in the baseline period.
Baseline Period (between visits 1 and 2) Eligible subjects entered an 8-week baseline period during which a seizure count was done. During this period, subjects and caregivers were contacted on a regular basis to ensure up to date information collection.
At the end of the baseline period, subjects who continued to be eligible were stratified based on previous therapy history (Early: previously treated with 2 to 5 AEDs versus Non-early: previously treated with >5 AEDs). Within each stratification, the investigator randomized each subject to receive one of the 2 treatments (VNS Therapy treatment or AED treatment) at the end of visit 2 using a randomization schedule provided by an independent third party (Synergos).
Implantation/AED Treatment Initiation (visit 3) For subjects randomized to the AED arm, a new AED treatment was initiated and gradually increased to an effective dose in accordance with the investigator's discretion and the manufacturer's suggested guidelines.
Subjects randomized to the VNS treatment arm were implanted with the VNS Therapy System and allowed adequate surgical recovery according to usual clinical practice before initiation of treatment. A delay of 2 weeks between the end of the baseline period and surgery was authorized to allow practical organization of the implantation. Extension of this period was approved in advance by the Study Director or his delegate.
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
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Refractory seizures
- •Having tried at least two appropriate anti-epileptic drugs (AEDs) tested to tolerance or to blood levels at upper end of the target range of which at least 2 have been tolerated at normal dose;
- •Having at least 3 appropriate AEDs left to try
- •Having his/her current AED medication at an optimal dose at baseline
- •At least three seizures per month (average over 2 months prior to admission), excluding absences.
- •No more than four (4) weeks between seizures (over 2 months prior to admission)
- •Age 17 years or less
- •Having been evaluated for epilepsy surgery and resective surgery not felt indicated or patient/parents/legal guardian declined.
- •Patient is a male or patient is a nonpregnant female adequately protected from conception. Females of childbearing potential must use an acceptable method of birth control. Abstinence is an acceptable means of birth control
- •Patient or legal guardian understands study procedures and has voluntarily signed an informed consent in accordance with institutional policies.
排除标准
- •Having tried less then 2 AEDs tested to tolerance or to blood levels at upper end of the target range of which at least 2 have been tolerated at normal doses in the patient's lifetime
- •A progressive neurological condition (e.g. brain tumor etc.)
- •Inability of the parents or reluctance of the child to comply with the frequency of clinic visits during the treatment phase
- •Patient has a history of noncompliance for seizure diary completion.
- •Patient has taken an investigational drug within a period of five times the mean elimination half-life of the investigational drug plus two weeks.
- •Patient is currently using another investigational device or drug.
- •Patient is likely to require a whole body Magnetic resonance imaging (MRI) after VNS Therapy device implantation. (Refer to the Physician's Manual for the NCP Generator for additional information on the use of MRI.)
- •Patient is currently receiving or likely to receive short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy after implantation (Refer to Physician's Manual for the VNS (Vagus Nerve Stimulation) Therapy device for additional information on the contraindicated use of diathermy).
- •Patient was previously enrolled in this or any other VNS Therapy device Study.
- •Patient has an active peptic ulcer
- •Patient has another unstable medical condition likely to precipitate seizures and make it difficult to evaluate to evaluate efficacy (e.g. diabetes)
- •Patient has had a unilateral or bilateral cervical vagotomy.
- •Patient is pregnant at the time of enrolment.
研究组 & 干预措施
Anti-Epileptic Drug (AED)
This arm will supply a comparison between VNS and new AEDs which is necessary to determine an overall treatment regimen for the 30% to 40% of patients who fail to respond to 2 AEDs.
干预措施: Anti-Epileptic Drug (AED) (Drug)
Vagus Nerve Stimulation (VNS) Therapy
Vagus Nerve Stimulation (VNS) Therapy is delivered by an implantable device similar to a pacemaker that sends mild stimulation to the left vagus nerve to help improve seizure control.
干预措施: Vagus Nerve Stimulation (VNS) Therapy (Device)
结局指标
主要结局
Proportion of Responders After 1 Year of Follow-up (ITT-population)
时间窗: 52 weeks post baseline
Responders are subjects who had no new AEDs added or significant dose changes in baseline AEDs within 1 year of follow-up, along with a reduction in the percentage change in seizure frequency from baseline to the 2-month period prior to the 1-year follow-up of at least 50%.
次要结局
- Mean Percent Change in Hague Seizure Severity Scale Score (ITT Population)(52 weeks post baseline)
- Wellcome Quality of Life Assessment (Questionnaire A) in Epilepsy (ITT Population)(52 weeks post baseline)
- Number of Subjects With Any Serious Adverse Events by System Organ Class & Preferred Term (Safety Population)(0-52 weeks)
- Hague Restriction in Childhood Epilepsy Scale (Questionnaire B) (ITT Population)(52 weeks post baseline)
- Mean Percent Change in Seizure Frequency (ITT Population)(52 weeks post baseline)
- Number of Subjects With Any Non-Serious Adverse Events by System Organ Class and Preferred Term (Safety Population)(0-52 weeks)