Ribavirin for treating Crimean Congo haemorrhagic fever.
Ribavirin for treating Crimean Congo haemorrhagic fever.
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DOI：
10.1002/14651858.cd012713.pub2
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发表时间：
2018-06-05
期刊：
影响因子：
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通讯作者：
Marshall R
中科院分区：
文献类型：
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作者：
Johnson S;Henschke N;Maayan N;Mills I;Buckley BS;Kakourou A;Marshall R
克里米亚刚果出血热是一种蜱传疾病，发生在亚洲、欧洲和非洲部分地区。自2000年以来，这种感染在土耳其、伊朗、俄罗斯、乌干达和巴基斯坦引起了流行病。高质量的一般支持性医疗服务有助于降低死亡率。抗病毒药物利巴韦林治疗CCHF存在不确定性和争议。评估利巴韦林治疗克里米亚-刚果出血热的效果。我们检索了Cochrane传染病组专业登记；对照试验中央登记册（Central）；MEDLINE (PubMed);Embase(奥维德);科学引文索引‐扩展，社会科学引文索引，会议论文集（Web of Science）；和CINAHL （EBSCOHost）。我们还检索了WHO国际临床试验注册平台（ICTRP）和ClinicalTrials.gov上正在进行的试验。我们进行了截至2017年10月16日的所有搜索。我们还联系了该领域的专家，并从这些来源获得了进一步的研究。我们评估了评估利巴韦林在疑似或确诊克里米亚刚果出血热患者中的应用的研究。我们纳入随机对照试验（RCTs）；纳入超过10名参与者的非随机研究（NRSs），设计为具有比较器的队列研究；和病例对照研究。两位综述作者评估了入选资格、偏倚风险并提取了数据。对于非随机研究，我们使用ROBINS - I工具评估偏倚风险。主效应分析包括我们判断偏倚风险为低、中、高的所有研究。我们使用风险比（rr）总结了二分类结果，使用平均差异（MDs）总结了连续结果，并在适当的地方使用了meta分析。我们对主要结果存在严重偏倚风险的研究进行了辅助评估和分析，因为这些研究经常被引用来支持使用利巴韦林。在主效应分析中，有5项研究符合我们的纳入标准：1项随机对照试验纳入136名受试者，4项非随机研究纳入612名受试者。我们排除了18项具有严重偏倚风险的非随机研究，其中没有一项研究试图控制混杂。我们不知道利巴韦林是否能降低死亡率(1项RCT； RR 1.13, 95%可信区间（CI） 0.29至4.32；136名参与者;极低确定性证据；3项非随机研究；RR 0.72, 95% CI 0.41 ~ 1.28；549名参与者;极低确定性证据)。我们不知道利巴韦林是否能缩短住院时间(1项随机对照试验：平均差（MD） 0.70天，95% CI‐0.39至1.79；136名参与者;1项非随机研究：MD = 0.80, 95% CI = 2.70 - 1.10；50个参与者;极低确定性证据)。我们不知道它是否降低了患者需要血小板输注的风险（1项RCT: RR 1.23, 95% CI 0.77 - 1.96； 136名受试者；极低确定性证据）。对于不良反应（包括溶血性贫血和需要停止治疗），由于数据不足，我们不知道利巴韦林是否会增加CCHF患者的风险。我们不知道在早期支持治疗中加入利巴韦林是否能改善结果。一项非随机研究评估了在症状出现后4天或更短时间内接受利巴韦林和支持性治疗的患者的死亡率，与症状出现后4天相比：接受早期支持性治疗和利巴韦林的组死亡率较低，但不可能区分单独使用利巴韦林和早期支持性医疗的效果。在辅助分析中，18项研究比较了接受利巴韦林和未接受利巴韦林的患者。由于混杂，所有的研究都有严重的偏倚风险，这反映在对利巴韦林有利的死亡率点估计上。我们不知道利巴韦林对治疗克里米亚刚果出血热是否有效。非随机研究经常被引用作为效果的证据，但这些研究的偏倚风险很高。更新回顾：在上一次检索（2017年10月16日）中发现的所有符合条件的已发表研究均纳入了利巴韦林治疗克里米亚刚果出血热。Cochrane综述的目的是发现利巴韦林是否是克里米亚刚果出血热的有效治疗方法。科克伦研究人员收集并分析了所有相关研究来回答这个问题。我们找到了23项研究。我们在这篇综述中纳入了五项有助于回答这个问题的研究。我们分析了其他18项研究，以帮助描述证据的局限性。没有足够的可靠证据表明利巴韦林对治疗克里米亚刚果出血热是否有效。一项随机临床试验可以帮助回答这个问题。这篇综述研究了什么？克里米亚刚果出血热（CCHF）是一种通过蜱叮咬传播的感染。在过去的15年里，这种情况变得越来越普遍，尤其是在土耳其和东欧的部分地区。慢性心力衰竭可能危及生命。对于患有严重CCHF的患者，最重要的护理方法是在医院密切监测他们，并向他们提供他们可能需要的任何液体或血液制品。利巴韦林是一种抗病毒药物，一些医生用它来治疗慢性心力衰竭。它广泛使用，通常是口服。关于是否需要利巴韦林治疗CCHF存在争议；一些人认为这是一种有效的治疗方法，或者如果及早服用会有所帮助，而另一些人则认为，就死亡风险、住院时间和药物本身的危害程度而言，它没有效果。总的来说，研究设计没有考虑到除了服用利巴韦林之外，干预组可能产生更好结果的因素，包括患者在诊断时的病情，或何时开始良好的支持性医疗护理。这使得利巴韦林和低死亡率之间的任何联系都存在问题。我们发现有5项研究考虑了可能混淆死亡风险与患者是否接受利巴韦林的重要因素。这些包括研究参与者的病情，他们接受了哪些其他护理，以及他们生病后多久接受了医疗护理。所有纳入的研究都在土耳其和伊朗进行，并将接受利巴韦林和支持治疗的CCHF患者与单独接受支持治疗的患者进行了比较。我们研究了与利巴韦林在CCHF中使用相关的五种不同结果，发现没有足够的可靠证据来确定利巴韦林是否有效。评论是最新的吗？综述作者检索了截至2017年10月16日发表的研究。
Crimean Congo haemorrhagic fever (CCHF) is a tick‐borne disease that occurs in parts of Asia, Europe and Africa. Since 2000 the infection has caused epidemics in Turkey, Iran, Russia, Uganda and Pakistan. Good‐quality general supportive medical care helps reduce mortality. There is uncertainty and controversy about treating CCHF with the antiviral drug ribavirin. To assess the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever. We searched the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (OVID); Science Citation Index‐Expanded, Social Sciences Citation index, conference proceedings (Web of Science); and CINAHL (EBSCOHost). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for trials in progress. We conducted all searches up to 16 October 2017. We also contacted experts in the field and obtained further studies from these sources. We evaluated studies assessing the use of ribavirin in people with suspected or confirmed Crimean Congo haemorrhagic fever. We included randomised control trials (RCTs); non‐randomised studies (NRSs) that included more than 10 participants designed as cohort studies with comparators; and case‐control studies. Two review authors assessed eligibility, risk of bias, and extracted data. For non‐randomized studies we used the ROBINS‐I tool to assess risk of bias. The main effects analysis included all studies where we judged the risk of bias to be low, moderate or high. We summarized dichotomous outcomes using risk ratios (RRs) and continuous outcomes using mean differences (MDs), and used meta‐analyses where appropriate. We carried out a subsidiary appraisal and analysis of studies with critical risk of bias for the primary outcome, as these are often cited to support using ribavirin. For the main effects analysis, five studies met our inclusion criteria: one RCT with 136 participants and four non‐randomized studies with 612 participants. We excluded 18 non‐randomized studies with critical risk of bias, where none had attempted to control for confounding. We do not know if ribavirin reduces mortality (1 RCT; RR 1.13, 95% confidence interval (CI) 0.29 to 4.32; 136 participants; very low‐certainty evidence; 3 non‐randomized studies; RR 0.72, 95% CI 0.41 to 1.28; 549 participants; very low‐certainty evidence). We do not know if ribavirin reduces the length of stay in hospital (1 RCT: mean difference (MD) 0.70 days, 95% CI ‐0.39 to 1.79; 136 participants; and 1 non‐randomized study: MD ‐0.80, 95% CI ‐2.70 to 1.10; 50 participants; very low‐certainty evidence). We do not know if it reduces the risk of patients needing platelet transfusions (1 RCT: RR 1.23, 95% CI 0.77 to 1.96; 136 participants; very low‐certainty evidence). For adverse effects (including haemolytic anaemia and a need to discontinue treatment), we do not know whether there is an increased risk with ribavirin in people with CCHF as data are insufficient. We do not know if adding ribavirin to early supportive care improves outcomes. One non‐randomized study assessed mortality in people receiving ribavirin and supportive care within four days or less from symptom onset compared to after four days since symptom onset: mortality was lower in the group receiving early supportive care and ribavirin, but it is not possible to distinguish between the effects of ribavirin and early supportive medical care alone. In the subsidiary analysis, 18 studies compared people receiving ribavirin with those not receiving ribavirin. All had a critical risk of bias due to confounding, reflected in the mortality point estimates favouring ribavirin. We do not know if ribavirin is effective for treating Crimean Congo haemorrhagic fever. Non‐randomized studies are often cited as evidence of an effect, but the risk of bias in these studies is high. 2 April 2019 Up to date All studies incorporated from most recent search Updated review: all eligible published studies found in the last search (16 Oct, 2017) were included Ribavirin for treating Crimean Congo haemorrhagic fever What is the aim of this review? The aim of this Cochrane review is to find out if ribavirin is an effective treatment for Crimean Congo haemorrhagic fever. Cochrane researchers collected and analysed all relevant studies to answer this question. We found 23 studies. We include five studies in this review that helped answer the question. We analysed the other 18 studies to help describe the limitations of the evidence. Key messages There is insufficient reliable evidence to show whether ribavirin is effective in treating Crimean Congo haemorrhagic fever. A randomised clinical trial could help answer this question. What was studied in the review? Crimean Congo haemorrhagic fever (CCHF) is an infection spread by tick bites. It has become more common in the last 15 years, particularly in Turkey and parts of Eastern Europe. CCHF can be life threatening. The most important way of caring for people who are seriously unwell with CCHF is to monitor them closely in hospital and give them any fluid or blood products they may need. Ribavirin is an antiviral drug that some doctors use to treat CCHF. It is widely available and is normally taken by mouth. There is debate over whether ribavirin is needed to treat CCHF; some argue that it is an effective treatment, or helps if given early, whilst others say that it has no effect, in terms of the risk of death, the length of time needed in hospital, and the extent of harm from the drug itself. Overall, the study designs did not take into account factors other than taking ribavirin that could result in better outcomes in the intervention group, including how ill the patient was when diagnosed, or when good supportive medical care was started. This made any association between ribavirin and lower mortality problematic. We found five studies that took into account important factors that could confound the risk of dying with whether or not a patient received ribavirin. These include how sick the study participants were, what other care they received, and how long after they became sick they received medical care. All included studies were conducted in Turkey and Iran, and compared people with CCHF who received ribavirin and supportive care to those who received supportive care alone. We looked at five different outcomes relating to ribavirin use in CCHF, and found that there is insufficient reliable evidence to determine whether ribavirin is effective. How up to date is the review? The review authors searched for studies that had been published up to 16 October 2017.