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Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial

INTRODUCTION: The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. METHODS: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the e...

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Autores principales: Tsiakos, Konstantinos, Tsakiris, Antonios, Tsibris, Georgios, Voutsinas, Pantazis-Michael, Panagopoulos, Periklis, Kosmidou, Maria, Petrakis, Vasileios, Gravvani, Areti, Gkavogianni, Theologia, Klouras, Eleftherios, Katrini, Konstantina, Koufargyris, Panagiotis, Rapti, Iro, Karageorgos, Athanassios, Vrentzos, Emmanouil, Damoulari, Christina, Zarkada, Vagia, Sidiropoulou, Chrysanthi, Artemi, Sofia, Ioannidis, Anastasios, Papapostolou, Androniki, Michelakis, Evangelos, Georgiopoulou, Maria, Myrodia, Dimitra-Melia, Tsiamalos, Panteleimon, Syrigos, Konstantinos, Chrysos, George, Nitsotolis, Thomas, Milionis, Haralampos, Poulakou, Garyphallia, Giamarellos-Bourboulis, Evangelos J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345236/
https://www.ncbi.nlm.nih.gov/pubmed/34363189
http://dx.doi.org/10.1007/s40121-021-00505-8
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author Tsiakos, Konstantinos
Tsakiris, Antonios
Tsibris, Georgios
Voutsinas, Pantazis-Michael
Panagopoulos, Periklis
Kosmidou, Maria
Petrakis, Vasileios
Gravvani, Areti
Gkavogianni, Theologia
Klouras, Eleftherios
Katrini, Konstantina
Koufargyris, Panagiotis
Rapti, Iro
Karageorgos, Athanassios
Vrentzos, Emmanouil
Damoulari, Christina
Zarkada, Vagia
Sidiropoulou, Chrysanthi
Artemi, Sofia
Ioannidis, Anastasios
Papapostolou, Androniki
Michelakis, Evangelos
Georgiopoulou, Maria
Myrodia, Dimitra-Melia
Tsiamalos, Panteleimon
Syrigos, Konstantinos
Chrysos, George
Nitsotolis, Thomas
Milionis, Haralampos
Poulakou, Garyphallia
Giamarellos-Bourboulis, Evangelos J.
author_facet Tsiakos, Konstantinos
Tsakiris, Antonios
Tsibris, Georgios
Voutsinas, Pantazis-Michael
Panagopoulos, Periklis
Kosmidou, Maria
Petrakis, Vasileios
Gravvani, Areti
Gkavogianni, Theologia
Klouras, Eleftherios
Katrini, Konstantina
Koufargyris, Panagiotis
Rapti, Iro
Karageorgos, Athanassios
Vrentzos, Emmanouil
Damoulari, Christina
Zarkada, Vagia
Sidiropoulou, Chrysanthi
Artemi, Sofia
Ioannidis, Anastasios
Papapostolou, Androniki
Michelakis, Evangelos
Georgiopoulou, Maria
Myrodia, Dimitra-Melia
Tsiamalos, Panteleimon
Syrigos, Konstantinos
Chrysos, George
Nitsotolis, Thomas
Milionis, Haralampos
Poulakou, Garyphallia
Giamarellos-Bourboulis, Evangelos J.
author_sort Tsiakos, Konstantinos
collection PubMed
description INTRODUCTION: The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. METHODS: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. RESULTS: The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1–92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. CONCLUSIONS: Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04398004 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40121-021-00505-8.
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spelling pubmed-83452362021-08-09 Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial Tsiakos, Konstantinos Tsakiris, Antonios Tsibris, Georgios Voutsinas, Pantazis-Michael Panagopoulos, Periklis Kosmidou, Maria Petrakis, Vasileios Gravvani, Areti Gkavogianni, Theologia Klouras, Eleftherios Katrini, Konstantina Koufargyris, Panagiotis Rapti, Iro Karageorgos, Athanassios Vrentzos, Emmanouil Damoulari, Christina Zarkada, Vagia Sidiropoulou, Chrysanthi Artemi, Sofia Ioannidis, Anastasios Papapostolou, Androniki Michelakis, Evangelos Georgiopoulou, Maria Myrodia, Dimitra-Melia Tsiamalos, Panteleimon Syrigos, Konstantinos Chrysos, George Nitsotolis, Thomas Milionis, Haralampos Poulakou, Garyphallia Giamarellos-Bourboulis, Evangelos J. Infect Dis Ther Original Research INTRODUCTION: The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. METHODS: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. RESULTS: The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1–92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. CONCLUSIONS: Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04398004 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40121-021-00505-8. Springer Healthcare 2021-08-06 2021-12 /pmc/articles/PMC8345236/ /pubmed/34363189 http://dx.doi.org/10.1007/s40121-021-00505-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research
Tsiakos, Konstantinos
Tsakiris, Antonios
Tsibris, Georgios
Voutsinas, Pantazis-Michael
Panagopoulos, Periklis
Kosmidou, Maria
Petrakis, Vasileios
Gravvani, Areti
Gkavogianni, Theologia
Klouras, Eleftherios
Katrini, Konstantina
Koufargyris, Panagiotis
Rapti, Iro
Karageorgos, Athanassios
Vrentzos, Emmanouil
Damoulari, Christina
Zarkada, Vagia
Sidiropoulou, Chrysanthi
Artemi, Sofia
Ioannidis, Anastasios
Papapostolou, Androniki
Michelakis, Evangelos
Georgiopoulou, Maria
Myrodia, Dimitra-Melia
Tsiamalos, Panteleimon
Syrigos, Konstantinos
Chrysos, George
Nitsotolis, Thomas
Milionis, Haralampos
Poulakou, Garyphallia
Giamarellos-Bourboulis, Evangelos J.
Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial
title Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial
title_full Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial
title_fullStr Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial
title_full_unstemmed Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial
title_short Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial
title_sort early start of oral clarithromycin is associated with better outcome in covid-19 of moderate severity: the achieve open-label single-arm trial
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345236/
https://www.ncbi.nlm.nih.gov/pubmed/34363189
http://dx.doi.org/10.1007/s40121-021-00505-8
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