Abstract

Objective: A recent case-series described patients with ALS to improve and/or stabilize after treatment with intravenous high-dose Penicillin G/Hydrocortisone (PenGH). In this study, we determine the safety and efficacy of intravenous PenGH versus placebo in combination with riluzole in patients with ALS.

Methods: Patients diagnosed with ALS according to the El Escorial criteria were randomized double-blind to four quarterly cycles of 21 d of intravenous PenGH or placebo in a 5:3 ratio. The primary outcome was change from baseline to week 48 in Amyotrophic Lateral Sclerosis Functional Rating Scale—Revised (ALSFRS-R). Secondary outcomes were lung function, muscle strength, plasma creatinine, clinical stage, gastrostomy placement, quality of life and occurrence of adverse of events.

Results: In total, 16 patients were randomized (10 PenGH and 6 placebo), of which 6 (40%) completed the study. Patients treated with PenGH progressed with 2.2 (95% CI 1.1–3.3) ALSFRS-R points per month and PenGH treatment did not halt disease progression (p = 0.002). No significant differences were found between PenGH or placebo (mean difference 0.5, 95% CI −1.01 to ∞, p = 0.28). Although PenGH was well-tolerated, 6 patients (38%, 3 in each arm) had thrombotic complications due to the intravenous administration method.

Conclusions: Treatment with PenGH does not halt disease or reverse progression in patients with ALS and showed no statistical difference with those who received placebo. Prolonged intravenous administration therapies may inflate thrombosis risk.

摘要

目的：最近的一个病例系列描述了 ALS 患者在接受静脉大剂量青霉素 G/氢化可的松 (PenGH) 治疗后得到改善和/或稳定。在这项研究中，我们确定静脉注射 PenGH 与安慰剂联合利鲁唑治疗 ALS 患者的安全性和有效性。

方法：根据 El Escorial 标准诊断为 ALS 的患者被随机双盲分配到四个季度周期的 21 天静脉注射 PenGH 或安慰剂，比例为 5:3。主要结果是肌萎缩侧索硬化功能评定量表 - 修订版 (ALSFRS-R) 从基线到第 48 周的变化。次要结果是肺功能、肌肉力量、血浆肌酐、临床分期、胃造口术位置、生活质量和不良事件的发生。

结果：总共有 16 名患者被随机分组​​（10 名 PenGH 和 6 名安慰剂），其中 6 名（40%）完成了研究。接受 PenGH 治疗的患者每月进展 2.2 (95% CI 1.1–3.3) ALSFRS-R 点，并且 PenGH 治疗并未阻止疾病进展 ( p  = 0.002)。PenGH 或安慰剂之间未发现显着差异（平均差异 0.5, 95% CI -1.01 至∞， p  = 0.28）。尽管 PenGH 耐受性良好，但仍有 6 名患者（38%，每组 3 名）因静脉给药方法而出现血栓并发症。

结论： PenGH 治疗不会阻止 ALS 患者的疾病或逆转进展，并且与接受安慰剂的患者没有统计学差异。长时间的静脉给药治疗可能会增加血栓形成的风险。