Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America
Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America
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DOI：
10.1086/425007
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发表时间：
2004-11-01
影响因子：
11.8
通讯作者：
Whitley, RJ
中科院分区：
文献类型：
--
作者：
Mertz, GJ;Miedzinski, L;Whitley, RJ
背景资料。利巴韦林在体外具有抗汉坦病毒的活性，但静脉注射利巴韦林治疗汉坦病毒心肺综合征(HCPS)的开放试验结果尚无定论。疑似先兆期或心肺期但无休克的患者可随机接受静脉注射利巴韦林(33 mg/kg[小于或等于2g]，随后每6小时注射16 mg/kg[小于或等于1 g]，连续4天；8 mg/kg[小于或等于5 g]，每8小时注射一次，持续3天)或安慰剂(连续7天或直到最初的新诺贝氏病毒抗体检测结果确认为阴性)。主要结果是在研究的第28天没有需要体外膜氧合(ECMO)的情况下存活。从1996年3月到2001年7月，36名受试者参加了试验，在这一点上，由于受试者的缓慢累积速度和无效分析的结果，研究提前终止。在纳入的36名受试者中，有23人(所有人都是在HCPS的心肺阶段登记)经血清学检测确诊为HCPS。在接受利巴韦林治疗的10名HCPS受试者和接受安慰剂治疗的13名HCPS受试者中，进入研究的疾病严重程度相似。在利巴韦林接受者和安慰剂接受者中，存活和不需要ECMO的受试者的比例相似(分别为70%和62%)；2名利巴韦林接受者和2名安慰剂接受者死亡，其中包括7名接受ECMO治疗的受试者中的3人。治疗组之间包括贫血在内的不良事件的发生频率相似。本研究中受试者的累积率不足以清楚地评估利巴韦林治疗HCPS的安全性或有效性。然而，利巴韦林耐受性良好，而且缺乏支持静脉使用利巴韦林的趋势，这表明它在治疗心肺阶段的HCPS可能无效。
Background. Ribavirin is active in vitro against hantaviruses, but the findings of an open trial of the use of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome (HCPS) were inconclusive.Methods. Subjects with suspected HCPS in the prodrome or cardiopulmonary phase but without shock were eligible for randomization to receive either intravenous ribavirin (33 mg/kg [less than or equal to 2 g], followed by 16 mg/kg [less than or equal to 1 g] given every 6 h for 4 days and by 8 mg/kg [less than or equal to .5 g] given every 8 h for 3 days) or placebo (administered for 7 days or until the initial Sin Nombre virus antibody test result was confirmed to be negative). The primary outcome was survival at day 28 of the study without the need for extracorporeal membrane oxygenation (ECMO).Results. Thirty-six subjects were enrolled in the trial from March 1996 through July 2001, at which point the study was terminated prematurely because of both the slow rate of accrual of subjects and the findings of a futility analysis. Of the 36 subjects enrolled, 23 (all of whom were enrolled during the cardiopulmonary stage of HCPS) had HCPS confirmed by serologic testing. The severity of illness at entry into the study was similar among the 10 subjects with HCPS who received ribavirin and the 13 subjects with HCPS who received placebo. The proportion of subjects who survived and who did not require ECMO was similar among ribavirin recipients and placebo recipients (70% vs. 62%, respectively); 2 ribavirin recipients and 2 placebo recipients died, including 3 of 7 subjects treated with ECMO. The frequency of adverse events, including anemia, was similar between treatment groups.Conclusions. The rate of accrual of subjects in the present study was inadequate to clearly assess the safety or efficacy of ribavirin in the treatment of HCPS. However, ribavirin was well tolerated, and the lack of trends supporting the use of intravenous ribavirin suggests that it is probably ineffective in the treatment of HCPS in the cardiopulmonary stage.