【Cochrane简语概要】伊维菌素 (Ivermectin) 治疗COVID-19有效吗？

关键信息

我们未发现有证据支持用伊维菌素治疗或预防 COVID-19，而研究基础也有限。

有 31 项正在进行的研究对伊维菌素进行评价，我们会在有相关研究结果时更新此综述。

（图片来源于news.pindula.co.zw）

伊维菌素是什么？

伊维菌素是一种用于治疗寄生虫如动物肠道寄生虫和人类疥疮 (scabies) 的药物。该药价格低廉，世界各地的寄生虫感染多发区有广泛应用。它没有什么不良反应。

实验室检查显示，伊维菌素可以减缓 COVID-19 (SARS-CoV-2) 病毒的复制，用到人体则需要很大剂量才能达到此效果。尚没有医疗监管机构批准使用伊维菌素治疗 COVID-19。该药仅可用于设计良好的研究（称为随机对照临床试验）以评估其潜在疗效。

我们想发现什么？

我们想知道，伊维菌素是否可降低 COVID-19 患者的死亡率、病症以及感染时间，或者是否可用于预访该病。我们纳入的研究，是对伊维菌素和安慰剂（哑治疗）、不治疗、常规照护或已有某种认识的其他治疗（如瑞德西韦或地塞米松）进行了比较。我们排除的研究，是对伊维菌素与不能有效治疗或不知道能否有效治疗 COVID-19 的药物进行了比较。

我们评估了伊维菌素在感染者中的效果：

– 人员死亡；
– COVID-19 病患症狀是好转或恶化；
– 不良反应；
– 入院或住院时间；
– 病毒清除。

预防上，我们找寻了有关预防COVID-19和SARS-CoV-2感染的效果证据。

我们做了什么？

我们检索了采用伊维菌素进行人体COVID-19预防或治疗的随机对照临床试验。接受伊维菌素治疗的是经实验室检查确诊的COVID-19 者，正在接受住院或门诊治疗。

我们对相关结果进行了比较和总括，并根据常用的证据可靠程度标准评价证据的质量级别。

我们发现了什么？

我们找到了14项研究，共涉及1678名受试者，这些研究对伊维菌素与不治疗、安慰剂或常规照护进行了比较。

治疗上，9项研究针对中度COVID-19住院者，4 项则针对中度COVID-19门诊患者。这些研究所用伊维菌素剂量和治疗持续时间存在差异。有1项研究针对COVID-19感染预防。

我们还发现了31项正在进行的研究，有18项研究有待作者进行分类或是尚未发表。

主要结果

治疗住院COVID-19患者

我们不知道，与安慰剂或常规照护相比，伊维菌素是否能于治疗后28天内：

– 造成更多或较少的患者死亡 (2项研究共 185 名患者)；
– 加重或改善患者病况，根据对人工通气 (2项研究共185名患者) 或氧气 (1项研究共45名患者)的需要进行评估；
– 增加或减少不良反应 (1项研究共152名患者)。

治疗后7天，我们也不知道，伊维菌素是否于治疗后7天内：

– 增加或降低COVID-19的阴性检出率 (2项研究共159名患者)。

与安慰剂或常规照护相比，治疗后28天内，伊维菌素可能不会改善患者的病况或是对患者的病况没有多少改善（1项研究共73名患者），对住院时间的影响亦是如此（1项研究共45名患者）。

治疗COVID-19门诊患者

我们不知道，与安慰剂或常规照护相比，伊维菌素是否会在：

– 治疗28天内，造成更多或较少的患者死亡 (2项研究共185名患者)；
– 治疗14天内，加重或改善患者病况，根据 根据对人工通气或氧气的需要进行评估(1项研究共398名患者)；
– 治疗7天内，增加或降低COVID-19的阴性检出率 (1项研究共24名患者)。

与安慰剂或常规照护相比，伊维菌素治疗14天内，门诊患者的的病况没有改善或是没有多少改善（1项研究共398名患者），对治疗28天内的不良反应的影响亦是如此（2项研究共422名患者）。

未见有研究观测门诊患者的入院情况。

预防COVID-19

我们不知道，与不用药物治疗相比，伊维菌素是否造成更多或较少的死亡（1项研究共304名患者），未见有受试者于治疗28天内死亡。该研究报告了COVID-19症状（并未确诊感染 SARS-CoV-2）和不良反应的发生，但所报告的方式使我们无法将其纳入分析中。该研究并未观测入院情况。

证据的局限性有哪些？

我们的证据质量非常低，因为我们仅纳入了14项并没有多少受试者、也没有多少事件（如死亡或人工通气需要）的研究。各研究所用方法不同，也未对我们所感兴趣的每件事（如生活质量）都进行报告。

证据的更新时效如何？

证据更新至 2021年5月26日。

结论: 

根据目前可见的极低至低质量证据，我们不确定伊维菌素用于治疗或预防 COVID-19 的有效性和安全性。已完成的研究数量较少，且没有多少高质量证据。有几项研究仍在进行中，更新综述时可能会有更清晰的答案。总体而言，现有的可靠证据不支持在精心设计的随机临床试验之外使用伊维菌素治疗或预防 COVID-19。

作者: Popp M, Stegemann M, Metzendorf M-I, Gould S, Kranke P, Meybohm P, Skoetz N, Weibel S；译者：臧渝梨，Cochrane Hong Kong, 香港中文大学医学院那打素护理学院； 审校：李迅，Cochrane中国协作网成员单位，北京中医药大学循证医学中心；编辑排版：张晓雯、索于思，Cochrane中国协作网成员单位，北京中医药大学循证医学中心

相关文章链接

【Cochrane Plain Language Summary】Is ivermectin effective for COVID-19?

Key messages

We found no evidence to support the use of ivermectin for treating or preventing COVID-19 infection, but the evidence base is limited.

Evaluation of ivermectin is continuing in 31 ongoing studies, and we will update this review with their results when they become available. 

What is ivermectin?

Ivermectin is a medicine used to treat parasites such as intestinal parasites in animals and scabies in humans. It is cheap and is widely used in regions of the world where parasitic infestations are common. It has few unwanted effects. 

Tests in the laboratory show ivermectin can slow the reproduction of the COVID-19 (SARS-CoV-2) virus but such effects would need major doses in humans. Medical regulators have not approved ivermectin for COVID-19. It should only be used as part of well-designed studies (called randomized controlled trials) evaluating potential effects. 

What did we want to find out?

We wanted to know if ivermectin reduces death, illness, and length of infection in people with COVID-19, or is useful in prevention of the disease. We included studies comparing the medicine to placebo (dummy treatment), no treatment, usual care, or treatments for COVID-19 that are known to work to some extent, such as remdesivir or dexamethasone. We excluded studies that compared ivermectin to other drugs that do not work, such as hydroxychloroquine, or that are not known to be effective against COVID-19.

We evaluated the effects of ivermectin in infected people on:

– people dying;
– whether people's COVID-19 symptoms got better or worse; 
– unwanted effects;
– hospital admission or time in hospital; 
– viral clearance.

For prevention, we sought the effect on preventing COVID-19 and SARS-CoV-2 infection.

What did we do? 

We searched for randomized controlled trials that investigated ivermectin to prevent or treat COVID-19 in humans. People being treated with ivermectin had to have laboratory-test confirmed COVID-19 and be receiving treatment in hospital or as outpatients.

We compared and summarized the results of the studies and rated our confidence in the evidence, based on common criteria as to how reliable the evidence is.

What did we find? 

We found 14 studies with 1678 participants that investigated ivermectin compared to no treatment, placebo, or usual care.

For treatment, there were nine studies of people with moderate COVID-19 in hospital and four of outpatients with mild COVID-19. The studies used different doses of ivermectin and different durations of treatment.

One study investigated ivermectin to prevent COVID-19.

We also found 31 ongoing studies, and there are 18 studies still requiring clarification from the authors or not yet published.

Main results 

Treating people in hospital with COVID-19

We don't know whether ivermectin compared with placebo or usual care, 28 days after treatment:

– leads to more or fewer deaths (2 studies, 185 people); 
– worsens or improves patients' condition assessed by need for ventilation (2 studies, 185 people) or oxygen (1 study, 45 people); 
– increases or reduces unwanted events (1 study, 152 people).

Seven days after treatment, we don't know if ivermectin:

– increases or reduces negative COVID-19 tests (2 studies, 159 people).

Ivermectin compared to placebo or usual care may make little or no difference to improving patients' condition 28 days after treatment (1 study, 73 people) or to length of hospital stay (1 study, 45 people).

Treating outpatients with COVID-19

We don't know whether ivermectin compared with placebo or usual care:

– leads to more or fewer deaths 28 days after treatment (2 studies, 422 people); 
– worsens or improves patients' condition 14 days after treatment assessed by need for ventilation (1 study, 398 people); 
– increases or reduces negative COVID-19 tests seven days after treatment (1 study, 24 people).

Ivermectin compared to placebo or usual care may make little or no difference to improving outpatients' condition 14 days after treatment (1 study, 398 people) or to the number of unwanted events 28 days after treatment (2 studies, 422 people).

No studies looked at hospital admissions in outpatients.

Preventing COVID-19

We don't know whether ivermectin leads to more or fewer deaths compared with no drug (1 study, 304 people); no participant died 28 days after the drug. This study reported results for development of COVID-19 symptoms (but not confirmed SARS-CoV-2 infection) and unwanted events, but in a way that we could not include in our analyses. This study did not look at hospital admissions.

What are the limitations of the evidence?

Our confidence in the evidence is very low because we could only include 14 studies with few participants and few events, such as deaths or need for ventilation. The methods differed between studies, and they did not report everything we were interested in, such as quality of life. 

How up to date is this evidence?

The evidence is up to date to 26 May 2021.

Authors' conclusions: 

Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID-19. The completed studies are small and few are considered high quality. Several studies are underway that may produce clearer answers in review updates. Overall, the reliable evidence available does not support the use ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials.

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