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.
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