TREATMENT OF HANTAVIRAL CARDIOPULMONARY SYNDROME

在智利因汉坦病毒心肺综合征住院的患者中，病死率超过50%，而且尚无经证实有效的治疗方法。静脉注射利巴韦林在体外对汉坦病毒有活性，在对照试验中静脉注射利巴韦林降低了汉坦相关肾综合征出血热[HFRS]的死亡率。最近，NIAID协同抗病毒研究小组（G. Mertz， PI）启动了一项类似的利巴韦林用于疑似汉坦病毒感染早期治疗的安慰剂对照试验。如项目3所述，有强有力的证据表明HCPS的心肺休克阶段是免疫介导的，并且休克的严重程度与HLA类型有关。在朝鲜冲突期间进行的对照试验中，早期使用皮质类固醇治疗（在休克发作之前）降低了休克的严重程度，并显著降低了肾功能障碍的严重程度。最近，智利和阿根廷的医生在HCPS患者中使用了大剂量静脉注射甲基泼尼索龙，他们认为在休克发作前使用是有效的。我们假设利巴韦林和类固醇治疗可能是相加的，甚至是协同的。为了确定利巴韦林或类固醇治疗是否能降低HCPS患者的死亡率，将对疑似汉坦病毒感染的患者进行静脉注射利巴韦林和静脉注射皮质类固醇治疗的对照试验，采用2X2因子设计，分为四个研究组：安慰剂/安慰剂、利巴韦林/安慰剂、强的松龙/安慰剂和利巴韦林/强的松龙。入组标准、药物剂量、测量和终点将与casg在美国和加拿大赞助的试验一致，如果可能的话，还将与阿根廷正在考虑的试验一致。因此，我们将通过荟萃分析或通过调整研究地点的直接比较来提高我们评估药物疗效的能力。

Case fatality among persons hospitalized with hantavirus cardiopulmonary syndrome [HCPS] in Chile exceeds 50%, and there is not treatment with proven efficacy. Intravenous ribavirin is active against hantaviruses in vitro, and intravenous ribavirin administration decreased mortality in controlled trials in Hantaan-associated hemorrhagic fever with renal syndrome [HFRS]. A similar, placebo-controlled trial of ribavirin for the early treatment of suspected hantavirus infection has recently been initiated by the NIAID Collaborative Antiviral Study Group (G. Mertz, PI). As described in Project 3, there is strong evidence that cardiopulmonary shock phase of HCPS is immune mediated and that the severity of shock is associated with HLA type. In controlled trials done during the Korean conflict, early treatment with corticosteroid therapy (before the onset of shock) reduced the severity of shock and significantly reduced the severity of renal dysfunction. Recently physicians in Chile and Argentina have used high-dose, intravenous methylpredinsolone in persons with HCPS, and they believe it is effective when used before the onset of shock. We hypothesize that treatment with ribavirin and steroids may be additive or even synergistic. To determine whether ribavirin or steroid therapy reduces mortality in persons with HCPS, a controlled trial of intravenous ribavirin and intravenous corticosteroid treatment will be performed in persons with suspected hantavirus infection using a 2X2 factorial design with four study groups: placebo/placebo, ribavirin/placebo, prednisolone/placebo, and ribavirin/prednisolone. Entry criteria, drug dosing, measurements and endpoints will be consistent with those employed in the CASG-sponsored trial in the U.S. and Canada and, if possible, in trials under consideration in Argentina. As such, we will increase our ability to assess drug efficacy through meta-analyses or through direct comparison with adjustment for study site.