TREATMENT OF HANTAVIRAL CARDIOPULMONARY SYNDROME

智利汉坦病毒心肺综合征住院患者的病死率超过50%，目前还没有经过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效，在汉滩相关性肾综合征出血热[HFRS]的对照试验中，静脉注射利巴韦林可降低死亡率。NIAID合作抗病毒研究小组(G.Mertz，PI)最近启动了一项类似的安慰剂对照试验，用于早期治疗疑似汉坦病毒感染。正如项目3所述，有强有力的证据表明，HCPS的心肺休克期是由免疫介导的，休克的严重程度与人类白细胞抗原(HLA型)相关。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(在休克发生之前)可以降低休克的严重程度，并显著降低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的静脉注射甲基强的松龙，他们认为在休克发生之前使用是有效的。我们推测，利巴韦林和类固醇的治疗可能是相加的，甚至是协同的。为了确定利巴韦林或类固醇疗法是否能降低患有HCPS的患者的死亡率，将对疑似感染汉坦病毒的患者进行静脉注射利巴韦林和静脉皮质类固醇治疗的对照试验，采用2X2析因设计，有四个研究组：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。入选标准、药物剂量、测量方法和终点将与CASG在美国和加拿大赞助的试验中采用的一致，如果可能，也将与阿根廷正在考虑的试验中采用的一致。因此，我们将通过荟萃分析或通过与研究地点调整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.