Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype
Abstract Background The role of ivermectin in the treatment of COVID-19 is still under debate, yet the drug has been widely used in some parts of the world, as shown by impressive market data. The available body of evidence may have changed over the last months, as studies have been retracted and “s...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-07-01
|
| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12879-022-07589-8 |
| _version_ | 1818509732364681216 |
|---|---|
| author | Milena Soriano Marcolino Karina Cardoso Meira Nathalia Sernizon Guimarães Paula Perdigão Motta Victor Schulthais Chagas Silvana Márcia Bruschi Kelles Laura Caetano de Sá Reginaldo Aparecido Valacio Patrícia Klarmann Ziegelmann |
| author_facet | Milena Soriano Marcolino Karina Cardoso Meira Nathalia Sernizon Guimarães Paula Perdigão Motta Victor Schulthais Chagas Silvana Márcia Bruschi Kelles Laura Caetano de Sá Reginaldo Aparecido Valacio Patrícia Klarmann Ziegelmann |
| author_sort | Milena Soriano Marcolino |
| collection | DOAJ |
| description | Abstract Background The role of ivermectin in the treatment of COVID-19 is still under debate, yet the drug has been widely used in some parts of the world, as shown by impressive market data. The available body of evidence may have changed over the last months, as studies have been retracted and “standards of care” (SOC) used in control groups have changed with rapidly evolving knowledge on COVID-19. This review aims to summarize and critically appraise the evidence of randomized controlled trials (RCTs) of ivermectin, assessing clinical outcomes in COVID-19 patients. Methods RCTs evaluating the effects of ivermectin in adult patients with COVID-19 were searched through June 22, 2022, in four databases, L.OVE platform, clinical trial registries and pre-prints platforms. Primary endpoints included all-cause mortality and invasive ventilation requirement. Secondary endpoint was the occurrence of adverse events. Risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Meta-analysis included only studies which compared ivermectin to placebo or SOC. Random-effects were used to pool the risk ratios (RRs) of individual trials. The quality of evidence was evaluated using GRADE. The protocol was register in PROSPERO (CRD42021257471). Results Twenty-five RCTs fulfilled inclusion criteria (n = 6310). Of those, 14 compared ivermectin with placebo, in night ivermectin associated with SOC was compared to SOC and two studies compared ivermectin to an active comparator. Most RCTs had some concerns or high risk of bias, mostly due to lack of concealment of the randomization sequence and allocation, lack of blinding and high number of missing cases. Ivermectin did not show an effect in reducing mortality (RR = 0.76; 95%CI: 0.52–1.11) or mechanical ventilation (RR = 0.74; 95%CI: 0.48–1.16). This effect was consistent when comparing ivermectin vs. placebo, and ivermectin associated with SOC vs. SOC, as well as in sensitivity analysis. Additionally, there was very low quality of evidence regarding adverse effects (RR = 1.07; 95%CI: 0.84–1.35). Conclusions The evidence suggests that ivermectin does not reduce mortality risk and the risk of mechanical ventilation requirement. Although we did not observe an increase in the risk of adverse effects, the evidence is very uncertain regarding this endpoint. |
| first_indexed | 2024-12-10T22:49:26Z |
| format | Article |
| id | doaj.art-46c7f21761714a8f822e90e3b9d50ada |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-10T22:49:26Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-46c7f21761714a8f822e90e3b9d50ada2022-12-22T01:30:28ZengBMCBMC Infectious Diseases1471-23342022-07-0122112510.1186/s12879-022-07589-8Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hypeMilena Soriano Marcolino0Karina Cardoso Meira1Nathalia Sernizon Guimarães2Paula Perdigão Motta3Victor Schulthais Chagas4Silvana Márcia Bruschi Kelles5Laura Caetano de Sá6Reginaldo Aparecido Valacio7Patrícia Klarmann Ziegelmann8Department of Internal Medicine, Medical School and Telehealth Center, University Hospital, Universidade Federal de Minas GeraisHealth School, Federal University of Rio Grande do NorteInstituto de Saúde Coletiva da Universidade Federal da BahiaFaculdade de Farmácia da Universidade Federal de Minas GeraisDepartment of Internal Medicine, Medical School and Telehealth Center, University Hospital, Universidade Federal de Minas GeraisPontifícia Universidade Católica de Minas GeraisDepartment of Internal Medicine, Medical School and Telehealth Center, University Hospital, Universidade Federal de Minas GeraisHospital Metropolitano Odilon BehrensInstitute for Health Technology Assessment (IATS/CNPq)Abstract Background The role of ivermectin in the treatment of COVID-19 is still under debate, yet the drug has been widely used in some parts of the world, as shown by impressive market data. The available body of evidence may have changed over the last months, as studies have been retracted and “standards of care” (SOC) used in control groups have changed with rapidly evolving knowledge on COVID-19. This review aims to summarize and critically appraise the evidence of randomized controlled trials (RCTs) of ivermectin, assessing clinical outcomes in COVID-19 patients. Methods RCTs evaluating the effects of ivermectin in adult patients with COVID-19 were searched through June 22, 2022, in four databases, L.OVE platform, clinical trial registries and pre-prints platforms. Primary endpoints included all-cause mortality and invasive ventilation requirement. Secondary endpoint was the occurrence of adverse events. Risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Meta-analysis included only studies which compared ivermectin to placebo or SOC. Random-effects were used to pool the risk ratios (RRs) of individual trials. The quality of evidence was evaluated using GRADE. The protocol was register in PROSPERO (CRD42021257471). Results Twenty-five RCTs fulfilled inclusion criteria (n = 6310). Of those, 14 compared ivermectin with placebo, in night ivermectin associated with SOC was compared to SOC and two studies compared ivermectin to an active comparator. Most RCTs had some concerns or high risk of bias, mostly due to lack of concealment of the randomization sequence and allocation, lack of blinding and high number of missing cases. Ivermectin did not show an effect in reducing mortality (RR = 0.76; 95%CI: 0.52–1.11) or mechanical ventilation (RR = 0.74; 95%CI: 0.48–1.16). This effect was consistent when comparing ivermectin vs. placebo, and ivermectin associated with SOC vs. SOC, as well as in sensitivity analysis. Additionally, there was very low quality of evidence regarding adverse effects (RR = 1.07; 95%CI: 0.84–1.35). Conclusions The evidence suggests that ivermectin does not reduce mortality risk and the risk of mechanical ventilation requirement. Although we did not observe an increase in the risk of adverse effects, the evidence is very uncertain regarding this endpoint.https://doi.org/10.1186/s12879-022-07589-8COVID-19SARS-CoV-2Novel coronavirusTherapeuticsSystematic reviewMeta-analysis |
| spellingShingle | Milena Soriano Marcolino Karina Cardoso Meira Nathalia Sernizon Guimarães Paula Perdigão Motta Victor Schulthais Chagas Silvana Márcia Bruschi Kelles Laura Caetano de Sá Reginaldo Aparecido Valacio Patrícia Klarmann Ziegelmann Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype BMC Infectious Diseases COVID-19 SARS-CoV-2 Novel coronavirus Therapeutics Systematic review Meta-analysis |
| title | Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype |
| title_full | Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype |
| title_fullStr | Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype |
| title_full_unstemmed | Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype |
| title_short | Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype |
| title_sort | systematic review and meta analysis of ivermectin for treatment of covid 19 evidence beyond the hype |
| topic | COVID-19 SARS-CoV-2 Novel coronavirus Therapeutics Systematic review Meta-analysis |
| url | https://doi.org/10.1186/s12879-022-07589-8 |
| work_keys_str_mv | AT milenasorianomarcolino systematicreviewandmetaanalysisofivermectinfortreatmentofcovid19evidencebeyondthehype AT karinacardosomeira systematicreviewandmetaanalysisofivermectinfortreatmentofcovid19evidencebeyondthehype AT nathaliasernizonguimaraes systematicreviewandmetaanalysisofivermectinfortreatmentofcovid19evidencebeyondthehype AT paulaperdigaomotta systematicreviewandmetaanalysisofivermectinfortreatmentofcovid19evidencebeyondthehype AT victorschulthaischagas systematicreviewandmetaanalysisofivermectinfortreatmentofcovid19evidencebeyondthehype AT silvanamarciabruschikelles systematicreviewandmetaanalysisofivermectinfortreatmentofcovid19evidencebeyondthehype AT lauracaetanodesa systematicreviewandmetaanalysisofivermectinfortreatmentofcovid19evidencebeyondthehype AT reginaldoaparecidovalacio systematicreviewandmetaanalysisofivermectinfortreatmentofcovid19evidencebeyondthehype AT patriciaklarmannziegelmann systematicreviewandmetaanalysisofivermectinfortreatmentofcovid19evidencebeyondthehype |