This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Systematic Review
Andrew Hill
University of Liverpool
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved human subjects.
- The author confirmed that all appropriate ethical guidelines for the use of human subjects have been followed, any necessary IRB and/or ethics committee review has been obtained, and information about the IRB/ethics committee is included in the manuscript.
- The author has confirmed that all necessary patient/participant consent or assent has been obtained and the appropriate institutional forms have been archived. If the IRB/ethics committee waived the requirement for patient/participant consent or assent, an explanation for the waiver is included in the text.
- This study reports on a clinical trial.
- The author has confirmed that this trial has been registered with an ICMJE-approved registry, and the trial registration ID has been provided in the text. If the article reports on a study that was registered retrospectively, a statement explaining why the study was not registered in advance has been provided in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
EDITORIAL NOTE:
Editorial Note: On July 6, 2021, Open Forum Infectious Diseases published a version of this preprint. The authors subsequently learned that one of the studies on which this analysis was based had been withdrawn due to fraudulent data. An expression of concern was issued on August 9, 2021. The authors have submitted a revised version excluding the problematic study, and the originally published paper has been retracted. The revised version is now available at the journal.
Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.
Keywords
ivermectin, COVID-19, SARS-CoV-2
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Systematic Review
Andrew Hill
University of Liverpool
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Open Forum Infectious Diseases.
Version 1
Posted 19 Jan, 2021
Community comments: 18
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved human subjects.
- The author confirmed that all appropriate ethical guidelines for the use of human subjects have been followed, any necessary IRB and/or ethics committee review has been obtained, and information about the IRB/ethics committee is included in the manuscript.
- The author has confirmed that all necessary patient/participant consent or assent has been obtained and the appropriate institutional forms have been archived. If the IRB/ethics committee waived the requirement for patient/participant consent or assent, an explanation for the waiver is included in the text.
- This study reports on a clinical trial.
- The author has confirmed that this trial has been registered with an ICMJE-approved registry, and the trial registration ID has been provided in the text. If the article reports on a study that was registered retrospectively, a statement explaining why the study was not registered in advance has been provided in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
View the published article at Open Forum Infectious Diseases.
EDITORIAL NOTE:
Editorial Note: On July 6, 2021, Open Forum Infectious Diseases published a version of this preprint. The authors subsequently learned that one of the studies on which this analysis was based had been withdrawn due to fraudulent data. An expression of concern was issued on August 9, 2021. The authors have submitted a revised version excluding the problematic study, and the originally published paper has been retracted. The revised version is now available at the journal.
Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.
Figure 1
Figure 2
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