A Placebo-controlled Study of Efficacy & Safety of Aspirin as an add-on Treatment in Patients With Tuberous Sclerosis Complex (TSC) & Refractory Seizures
试验速览
- 阶段
- 2 期
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Percentage of reduction in seizure frequency
研究概览
简要总结
There had been much evidence in aspirin controlling tumorous conditions conducted by basic researches, especially through mammilian target of rapamycin (mTOR) pathway. The investigator observed efficacy of aspirin in the treatment of tuberous sclerosis complex (TSC) in one child who got Kawasaki disease and in the addition four TSC patients with epilepsy. The investigator intend to evaluate whether aspirin would be an effective add-on treatment in TSC patients with refractory seizures.
详细描述
There is no optional treatment for patients with tuberous sclerosis complex (TSC) and refractory epilepsy.The investigator observed efficacy of aspirin in the treatment of in one child who got Kawasaki disease. Subsequent adjunctive aspirin therapy in four patients yielded a reducted frequency of seizure for 51.2-89.7%. The investigator intend to evaluate whether aspirin would be an effective add-on treatment in TSC patients with refractory seizures.
Refractory epilepsy was defined as more than 8 times of epileptic events in 4 weeks at baseline, and had been given more than two antiepileptic drugs maintaining for more than 3 months.TSC patients aged 6-30 years' old would be recruited with refractory seizures and randomly assigned to two groups, aspirin and antiepileptic drugs(AEDS) group and placebo-AEDS group after written informed consent be obtained. Patients and their guardians would be instructed to record their own seizure diary on the epileptic events and report monthly.The primary outcome would be reduction of seizure frequency (measured by average seizure frequency and response rate). The secondary outcome would include seizure-free days, seizure-free rates, changes in EEG, changes of facial angiofibromas, and exposure-response relationship analysis.The study is designed as a placebo-controlled, randomized, blinded evaluation trial.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patients, investigators, site personnel, and the sponsor's study team were masked to treatment allocation, but allocation was not concealed from personnel in charge of drug supply, and implementation of the randomisation list. The Data Safety Monitoring Board (DSMB) independent statistician and programmer were semi-blind to treatment allocation at the time of DSMB meetings.
入排标准
- 年龄范围
- 6 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •6-30 years old TSC patients (by Gomez criteria)
- •more than 8 seizures occurred in the 4-week baseline time,with no continued seizure-free time of more than 10 days a month
- •more than two antiepileptic drugs (AED) had been administered but fail to control the situation; maintaining with 1 or more than 1 AEDS for over 2 months and intending to continue with the drugs
- •patients who had been treated with rapamycin should have been stopped for more than 3 months
- •vagus nerve stimulation (VNS) is allowed as a previous or current therapy and would maintain until the end of the trial
排除标准
- •Subependymal Giant Cell Astrocytoma and requires immediate surgery；
- •a history of intracranial surgery within 6 months;
- •epilepsy caused by improper use of drugs;
- •patients treated with aspirin had severe or intolerant side effects, including gastrointestinal ulcer, bleeding, aspirin allergy, and other conditions;
- •psychogenic seizures;
- •severe renal dysfunction and infection
- •pregnant women and lactating women
- •not regular follow-up
- •other: because when children and adolescents suffering from influenza or chickenpox, using aspirin may cause a rare life-threatening Reye syndrome (characterized with persistent vomiting）, should temporary withdrawal, medication needs to consult a physician before using again.
研究组 & 干预措施
experimental：asprin & AEDS
Aspirin 5mg/kg，maximum 300mg; once a day plus AEDS
干预措施: Aspirin (Drug)
experimental：asprin & AEDS
Aspirin 5mg/kg，maximum 300mg; once a day plus AEDS
干预措施: AED (Drug)
control: placebo & AEDS
placebo 5mg/kg，maximum 300mg; once a day plus AEDS
干预措施: AED (Drug)
control: placebo & AEDS
placebo 5mg/kg，maximum 300mg; once a day plus AEDS
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of reduction in seizure frequency
时间窗: Baseline phase (week 0); Observation phase week 1（±1 days）；Observation phase week 2（±2 days）；Observation phase week 4（±3 days）d；Observation phase week 8（±7 days）；Observation phase week 12（±14 days）
Estimated by median percentage of seizure frequency reduction and response rate comparing each group with the baseline; response rate is defined as more than 50% of reduction in seizure frequency. The seizure diary of individual participants would be recorded every day during the trial time by the participants and their guardians. The correct way of recording will be guided by investigator specialized in epileptic disease with discrimination of real or false seizure events. •seizure information was known within the same period of time (baseline or maintenance phase)
次要结局
- Total days of seizure free(Baseline, Week 0-4, Week 4-8, Week 8-12)
- Improvement of facial angiofibromas(Baseline, Week 4, Week 8, Week 12)
- Subjective evaluation of treatment-response condition(Baseline, Week 12)
- A mild reduction in seizure frequency(baseline, Week 12)
- Changes of epileptic discharges in electroencephalogram(Baseline, Week 12)
- Changes of cognitive condition(Baseline, Week 12)