Department of Pediatrics, West Virginia University Health Sciences Center, Charleston Division, Charleston, WV, USA.
Pediatr Infect Dis J. 2011 Oct;30(10):860-5. doi: 10.1097/INF.0b013e31821c922c.
La Crosse viral encephalitis (LACVE) is associated with residual epilepsy and neurocognitive deficits in survivors. This report summarizes 3 phases of clinical studies of children treated with intravenous (IV) ribavirin (RBV), each one exploring a different phase (I, IIA, IIB) of clinical trial development.
In phase I, 7 children with life-threatening LACVE were treated with emergency use RBV using a moderate IV dose (8.33 mg/kg/dose q 8 hours day 1, 5 mg/kg/dose q 8 hours days 2-10). In phase IIA, 12 children with severe LACVE were enrolled: 8 treated with RBV (same dose as phase I) and 4 with placebo. In phase IIB an escalated dose was used (33 mg/kg dose 1, then 16 mg/kg/dose q 6 hours for 4 days, and 8 mg/kg/dose q 8 hours for 3 days).
In a group of 15 children treated in phase I and phase IIA, RBV appeared safe at moderate dose, but based on steady-state RBV levels of 9.3 μM, estimated cerebrospinal fluid levels were less than 20% of the EC50 of RBV for LACVE. At the escalated dose used in phase IIB, adverse events occurred, likely related to RBV, and therefore the trial was discontinued. Nevertheless, valuable pharmacokinetic (PK) and safety data were obtained at moderate dose, with potential treatment implications for other indications.
Although the results do not support the use of RBV for LACVE, this nevertheless is the largest study of antiviral treatment for LACVE to date and the largest pharmacokinetic analysis of IV RBV in children for any indication.
拉科斯特病毒脑炎（LACVE）与幸存者的残留癫痫和神经认知缺陷有关。本报告总结了静脉内（IV）利巴韦林（RBV）治疗儿童的 3 个阶段临床研究，每个阶段都探索了临床试验开发的不同阶段（I、IIA、IIB）。
在 I 期，7 名患有危及生命的 LACVE 的儿童使用紧急使用 RBV 进行治疗，使用中等 IV 剂量（第 1 天 8 小时 8.33mg/kg/剂量，第 2-10 天 5mg/kg/剂量）。在 IIA 期，12 名患有严重 LACVE 的儿童入组：8 名接受 RBV 治疗（与 I 期相同剂量），4 名接受安慰剂治疗。在 IIB 期，使用了递增剂量（第 1 剂 33mg/kg，然后第 4 天 16mg/kg/剂量每 6 小时 1 次，第 3 天 8mg/kg/剂量每 8 小时 1 次）。
在 I 期和 IIA 期接受治疗的 15 名儿童中，RBV 中等剂量似乎是安全的，但基于 9.3μM 的稳态 RBV 水平，估计 RBV 的脑脊液水平不到 LACVE 的 EC50 的 20%。在 IIB 期使用递增剂量时，发生了不良反应，可能与 RBV 有关，因此试验被停止。尽管如此，在中等剂量下获得了有价值的药代动力学（PK）和安全性数据，这对其他适应症的治疗有潜在意义。
尽管结果不支持 RBV 用于 LACVE，但这是迄今为止最大的 LACVE 抗病毒治疗研究，也是最大的儿童 IV RBV 用于任何适应症的 PK 分析。
