Late Breaking Abstract - Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof of concept clinical trial

2021 ◽  
Author(s):  
Iwein Gyselinck ◽  
Robin Vos ◽  
Laurens Liesenborghs ◽  
Peter Verhamme ◽  
Wim Janssens
Keyword(s):  
Clinical Trial ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

scholarly journals Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Iwein Gyselinck ◽  
◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

scholarly journals A randomized, multicenter, open-label, adaptive, proof of concept clinical trial of new antivirals working against Sars-CoV2: Direct Antivirals Working against the Novel coronavirus – Azithromycin (DAWn-AZITHRO) trial

2020 ◽  
Author(s):  
Iwein Gyselinck ◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
Geert Verbeke ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background: The rapid emergence and the high disease burden of the novel coronavirus Sars-CoV-2 has created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against Sars-CoV-2 in vitro, and acts on cytokine signaling pathways that have been implicated in COVID-19.Methods: DAWn-Azithro is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID-wards are eligible for study-inclusion when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 hours through PCR (nasopharyngeal swab or bronchoalveolar lavage), or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. Primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days.Discussion: The trial investigates the urgent and still unmet global need for drugs that may impact on the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN-consortium, will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context.Trial registration: EU Clinical trials register, EudraCT Nb 2020-001614-38. Start date 2020-04-22.

scholarly journals Direct Antivirals Working against the Novel coronavirus – Azithromycin (DAWn-AZITHRO)A randomized, multicenter, open-label, adaptive, proof of concept clinical trial of new antivirals working against Sars-CoV2 – Azithromycin trial

2021 ◽  
Author(s):  
Iwein Gyselinck ◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
Geert Verbeke ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background: The rapid emergence and the high disease burden of the novel coronavirus Sars-CoV-2 has created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against Sars-CoV-2 in vitro, and acts on cytokine signaling pathways that have been implicated in COVID-19.Methods: DAWn-Azithro is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID-wards are eligible for study-inclusion when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 hours through PCR (nasopharyngeal swab or bronchoalveolar lavage), or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. Primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days.Discussion: The trial investigates the urgent and still unmet global need for drugs that may impact on the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN-consortium, will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context.Trial registration: EU Clinical trials register, EudraCT Nb 2020-001614-38. Start date 2020-04-22.

scholarly journals Correction to: Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Iwein Gyselinck ◽  
◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals A randomized, multicenter, open-label, adaptive, proof of concept clinical trial of new antivirals working against Sars-CoV2: Direct Antivirals Working against the Novel coronavirus – Azithromycin (DAWn-AZITHRO) trial

2020 ◽  
Author(s):  
Iwein Gyselinck ◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
Geert Verbeke ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background: The rapid emergence and the high disease burden of the novel coronavirus Sars-CoV-2 has created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against Sars-CoV-2 in vitro, and acts on cytokine signaling pathways that have been implicated in COVID-19.Methods: DAWn-Azithro is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID-wards are eligible for study-inclusion when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 hours through PCR (nasopharyngeal swab or bronchoalveolar lavage), or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. Primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days.Discussion: The trial investigates the urgent and still unmet global need for drugs that may impact on the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN-consortium, will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context.Trial registration: EU Clinical trials register, EudraCT Nb 2020-001614-38. Start date 2020-04-22.

scholarly journals Correction to: A randomized, open-label, adaptive, proof-of-concept clinical trial of modulation of host thromboinflammatory response in patients with COVID-19: the DAWn-Antico study

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
T. Vanassche ◽  
◽  
M. M. Engelen ◽  
Q. Van Thillo ◽  
J. Wauters ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Proof Of Concept ◽  
Open Label

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial

2020 ◽  
Author(s):  
Andrew A. Lover
Keyword(s):  
Clinical Trial ◽  
Scale Up ◽  
Secondary Analysis ◽  
Survival Models ◽  
Sufficient Evidence ◽  
Open Label ◽  
P Values ◽  
Randomized Controlled Studies ◽  
Wide Scale ◽  
Novel Coronavirus

AbstractHuman infections with a novel coronavirus (SARS-CoV-2) were first identified via syndromic surveillance in December of 2019 in Wuhan China. Since identification, infections (coronavirus disease-2019; COVID-19) caused by this novel pathogen have spread globally, with more than 250,000 confirmed cases as of March 21, 2020. An open-label clinical trial has just concluded, suggesting improved resolution of viremia with use of two existing therapies: hydroxychloroquine (HCQ) as monotherapy, and in combination with azithromycin (HCQ-AZ). [3, 4].The results of this important trial have major implications for global policy in the rapid scale-up and response to this pandemic. The authors present results with p-values for differences in proportions between the study arms, but their analysis is not able to provide effect size estimates.To address this gap, more modern analytical methods including survival models, have been applied to these data, and show modest to no impact of HCQ treatment, with more significant effects from the HCQ-AZ combination, potentially suggesting a role for co-infections in COVID-19 pathogenesis.The trial of Gautret and colleagues, with consideration of the effect sizes, and p-values from multiple models, does not provide sufficient evidence to support wide-scale rollout of HCQ monotherapy for the treatment of COVID-19; larger randomized studies should be considered. These data also suggest further randomized-controlled studies of HCQ-AZ combination therapy should be undertaken.

scholarly journals Is Machine Learning a Better Way to Identify COVID-19 Patients Who Might Benefit from Hydroxychloroquine Treatment?—The IDENTIFY Trial

2020 ◽  
Vol 9 (12) ◽  
pp. 3834
Author(s):  
Hoyt Burdick ◽  
Carson Lam ◽  
Samson Mataraso ◽  
Anna Siefkas ◽  
Gregory Braden ◽  
...  
Keyword(s):  
Machine Learning ◽  
Clinical Trial ◽  
Learning Algorithm ◽  
Pragmatic Trial ◽  
Therapeutic Agents ◽  
Study Endpoint ◽  
Machine Learning Algorithm ◽  
The Novel ◽  
Hazard Ratios ◽  
Novel Coronavirus

Therapeutic agents for the novel coronavirus disease 2019 (COVID-19) have been proposed, but evidence supporting their use is limited. A machine learning algorithm was developed in order to identify a subpopulation of COVID-19 patients for whom hydroxychloroquine was associated with improved survival; this population might be relevant for study in a clinical trial. A pragmatic trial was conducted at six United States hospitals. We enrolled COVID-19 patients that were admitted between 10 March and 4 June 2020. Treatment was not randomized. The study endpoint was mortality; discharge was a competing event. Hazard ratios were obtained on the entire population, and on the subpopulation indicated by the algorithm as suitable for treatment. A total of 290 patients were enrolled. In the subpopulation that was identified by the algorithm, hydroxychloroquine was associated with a statistically significant (p = 0.011) increase in survival (adjusted hazard ratio 0.29, 95% confidence interval (CI) 0.11–0.75). Adjusted survival among the algorithm indicated patients was 82.6% in the treated arm and 51.2% in the arm not treated. No association between treatment and mortality was observed in the general population. A 31% increase in survival at the end of the study was observed in a population of COVID-19 patients that were identified by a machine learning algorithm as having a better outcome with hydroxychloroquine treatment. Precision medicine approaches may be useful in identifying a subpopulation of COVID-19 patients more likely to be proven to benefit from hydroxychloroquine treatment in a clinical trial.

scholarly journals A SARS-CoV-2-ellenes antitestekkel végzett terápia helye a COVID–19 kezelésében

2021 ◽  
Vol 162 (51) ◽  
pp. 2030-2039
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Healthcare System ◽  
Neutralizing Antibodies ◽  
Therapeutic Option ◽  
Passive Immunization ◽  
Published Data ◽  
The Novel ◽  
Novel Coronavirus ◽  
Made In

Összefoglaló. Az új típusú koronavírus (SARS-CoV-2) okozta fertőzés és a COVID–19 elleni küzdelem egyik lehetősége a SARS-CoV-2-ellenes neutralizáló antitestekkel végzett passzív immunizáció. Az utóbbi időben számos készítmény jutott el a klinikai kipróbálásig. Az alábbiakban áttekintjük ezen készítmények legfőbb tulajdonságait és az antitest-terápiával elért klinikai eredményeket. Ezek alapján elsősorban prehospitálisan, az állapotprogresszió szempontjából leginkább veszélyeztetett populációnál alkalmazva, e készítmények jelentősen csökkenthetik az állapotromlás esélyét és a kórházi ellátás igényét, ezáltal javíthatják a kimenetelt, és mérsékelhetik az egészségügyi ellátórendszer terhelését. Orv Hetil. 2021; 162(51): 2030–2039. Summary. Passive immunization is a therapeutic option in the fight against the infection caused by the novel coronavirus (SARS-CoV-2) and COVID-19. Significant advances have been made in the development of SARS-CoV-2 neutralizing antibodies. Here we discuss the antibodies under clinical trial and the published data regarding their clinical efficacy. Based on these, when given to non-hospitalized patients at high risk for disease progression, these antibodies can significantly reduce worsening of the disease and the need for hospitalization. This can improve the outcomes of patients and help reduce the burden on the healthcare system. Orv Hetil. 2021; 162(51): 2030–2039.

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