Minneapolis Clinic of Neurology, Midwest Center for Seizure Disorders, Golden Valley, Minnesota, U.S.A.
Epilepsia. 2014 Sep;55(9):1444-51. doi: 10.1111/epi.12685. Epub 2014 Jun 25.
Part 1 of this phase III study was a randomized, double-blind, parallel-group, placebo-controlled, multicenter study of caregiver administered diazepam auto-injector (AI) in subjects with acute repetitive seizures (ARS) and demonstrated that diazepam AI was well-tolerated and significantly more effective than placebo AI in delaying the time to next seizure or rescue. Part 2 of this study, presented herein, was an open-label continuation to assess the long-term safety and effectiveness of diazepam AI for the treatment of ARS.
Of the 234 subjects randomized in part 1, 161 continued into part 2 and were provided open-label diazepam AI. Effectiveness measures were time to next seizure or rescue, number of subsequent rescues by type (rescue medication, emergency room visit, or other medical care), and number of subsequent seizures during the 12-h follow-up period. Safety data (adverse events and respirations <8/min) were also collected.
During the open-label part 2 study, 129 subjects were administered a total of 1,380 diazepam AI treatments (median 4.5; range 1-118), of which 1,071 (77.6%) were effective with no subsequent seizure or rescue during the 12-h follow-up period. Median number of subsequent seizures experienced by subjects was one (range 0-20). Of the 1,380 administrations, 79 (5.7%) required use of rescue medication, 18 (1.3%) required a visit to an emergency room, and 6 (0.4%) required other rescue medical care. In most (75%) of subjects with treatment-emergent adverse events (TEAEs), TEAEs were mild or moderate in severity. Commonly reported treatment-related TEAEs were injection-site pain (10.9%), injection-site hemorrhage (7%), and injection-site bruising (6.3%). Although three subjects met the predefined respiratory rate threshold, none were considered clinically significant or reported as AEs.
Long-term treatment with diazepam AI administered by trained caregivers in an outpatient setting to treat ARS is a safe and effective option. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
本研究第 1 部分为一项随机、双盲、平行组、安慰剂对照、多中心研究，旨在评估照料者给予地西泮自动注射器（AI）治疗急性重复发作性癫痫（ARS）的疗效，结果显示地西泮 AI 耐受性良好，与安慰剂 AI 相比，显著延迟了下一次癫痫发作或急救的时间。本研究第 2 部分为开放性标签延续研究，旨在评估地西泮 AI 治疗 ARS 的长期安全性和有效性。
在第 1 部分的 234 例随机患者中，161 例继续进入第 2 部分，接受开放性标签地西泮 AI 治疗。有效性评估指标包括下一次癫痫发作或急救的时间、随后根据类型（急救药物、急诊就诊或其他医疗护理）进行的后续急救次数，以及在 12 小时随访期间发生的后续癫痫发作次数。还收集了安全性数据（不良事件和呼吸频率<8/min）。
在开放性标签第 2 部分研究期间，129 例患者共接受了 1380 次地西泮 AI 治疗（中位数 4.5；范围 1-118），其中 1071 次（77.6%）有效，在 12 小时随访期间无后续癫痫发作或急救。患者随后发生癫痫发作的中位数为 1 次（范围 0-20）。在 1380 次给药中，79 次（5.7%）需要使用急救药物，18 次（1.3%）需要急诊就诊，6 次（0.4%）需要其他急救医疗护理。在大多数（75%）出现治疗中出现的不良事件（TEAE）的患者中，TEAE 的严重程度为轻度或中度。常见的治疗相关 TEAEs 为注射部位疼痛（10.9%）、注射部位出血（7%）和注射部位瘀伤（6.3%）。虽然有 3 例患者符合预设的呼吸频率阈值，但均未被认为具有临床意义或被报告为不良事件。
在门诊环境中，经过培训的照料者长期使用地西泮 AI 治疗 ARS 是一种安全有效的选择。本文的幻灯片摘要可在支持信息部分下载。
