Fampridine and Acetazolamide in EA2 and Related Familial EA A Prospective Randomized Placebo-Controlled Trial
Fampridine and Acetazolamide in EA2 and Related Familial EA A Prospective Randomized Placebo-Controlled Trial
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DOI：
10.1212/cpj.0000000000001017
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发表时间：
2021-08-01
影响因子：
2.2
通讯作者：
Strupp, Michael
中科院分区：
文献类型：
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作者：
Muth, Carolin;Teufel, Julian;Strupp, Michael
目的探讨缓释法吡啶和乙酰唑胺治疗发作性共济失调2型(EA2)患者的疗效和安全性。方法30例EA2患者随机分为3期交叉试验，其中女性8例，年龄20~71岁，18例，阳性家族史4例，临床诊断8例。每个周期持续12周，其中4周为冲洗期。每个患者接受20 mg/d的法普利定、750 mg/d的乙酰唑胺和安慰剂的随机序列治疗。主要终点是12周治疗期内最后30天内的发作次数。结果与安慰剂相比，法普利定的发作次数减少到63%(95%可信区间54%~74%)，乙酰唑胺发作次数减少到52%(95%可信区间46%~60%)。服用法普利定的患者共发生不良反应39例(26.5%)，其中乙酰唑胺治疗组66例(44.9%)(主要是味觉障碍和胃肠道不适)，安慰剂组42例(28.6%)。结论与安慰剂相比，法普利定和乙酰唑胺均能显著减少EA2及相关EA患者的发作次数。法普利定每日2次，每次10 mg，与乙酰唑胺250 mg，每日3次相比，副作用较少。该试验在DRKS.de(DRKS00005258)和EudraCT(2013-000107-17)注册。这项研究得到了联邦教育和研究部(BMBF)的支持(资助号为01EO0901)。法普利定(研究用药)由Biogen Idec.证据分类II类证据提供。
ObjectiveTo determine the efficacy and safety of the treatment with prolonged-release 4-aminopyridine (fampridine) and acetazolamide for patients with episodic ataxia type 2 (EA2), patients with EA2 were treated with a random sequence of fampridine, acetazolamide, and placebo in a 3-period crossover trial.MethodsA total of 30 patients with EA2 (8 female; aged 20-71 years; 18 genetically confirmed, 4 with a positive family history, 8 with the clinical diagnosis) were enrolled in this phase III, randomized, double-blind, placebo-controlled, 3-period crossover trial. Each period lasted 12 weeks with a 4-week washout period. Each patient received a random sequence of 20 mg/d fampridine, 750 mg/d acetazolamide, and placebo. The primary end point was the number of attacks during the last 30 days within the 12-week treatment period. Participants, caregivers, and those assessing the outcomes were blinded to the intervention.ResultsCompared with placebo, fampridine reduced the number of attacks to 63% (95% CI 54%-74%) and acetazolamide to 52% (95% CI 46%-60%). A total of 39 (26.5%) adverse events were observed under treatment with fampridine (mostly tingling paresthesia and fatigue), 66 (44.9%) happened under acetazolamide (mostly taste disturbance and gastrointestinal complaints), and 42 (28.6%) under placebo (mostly gastrointestinal complaints).ConclusionBoth fampridine and acetazolamide significantly reduce the number of attacks in patients with EA2 and related EA in comparison to placebo. Fampridine 10 mg twice daily had fewer side effects than acetazolamide 250 mg 3 times daily. The trial was registered with DRKS.de (DRKS00005258) and EudraCT (2013-000107-17). This study was supported by the Federal Ministry of Education and Research (BMBF) (grant number 01EO0901). Fampridine (study medication) was provided by Biogen Idec.Classification of EvidenceClass II evidence.