Azithromycin for treatment of hospitalised COVID-19 patients: a randomised, multicentre, open-label clinical trial (DAWn-AZITHRO)

Abstract

Background and objectivesAzithromycin was rapidly adopted as a repurposed drug to treat COVID-19 early in the pandemic. We aimed to evaluate its efficacy in patients hospitalised for COVID-19.MethodsIn a series of randomised, open-label, phase 2 proof-of-concept, multicenter clinical trials (Direct Antivirals Working against the novel Coronavirus [DAWn]), several treatments were compared with standard of care. In 15 Belgian hospitals, patients hospitalised with moderate to severe COVID-19 patients were allocated 2:1 to receive standard of care plus azithromycin or standard of care alone. The primary outcome was time to live discharge or sustained clinical improvement, defined as a two-point improvement on the WHO ordinal scale sustained for at least 3 days.ResultsPatients were included between April 22 and December 17, 2020. When 15-day follow-up data were available for 160 patients (56% of preset cohort), an interim analysis was performed at request of the independent Data Safety and Monitoring Board. Subsequently, DAWn-AZITHRO was stopped for futility. In total, 121 patients were allocated to the treatment arm and 64 patients to the standard of care arm. We found no effect of azithromycin on the primary outcome with Hazard ratio of 1.044 (95% confidence interval, 0.772–1.413; p=0.7798). None of the predefined subgroups showed significant interaction as covariates in the Fine-Gray regression analysis. No benefit of azithromycin was found on any of the short- and longer-term secondary outcomes.ConclusionTime to clinical improvement is not influenced by azithromycin in patients hospitalised with moderate to severe COVID-19.

Major adverse cardiovascular events (MACE) in patients with severe COVID-19 registered in the ISARIC WHO clinical characterization protocol: A prospective, multinational, observational study

“…Macrolide treatment was widely recommended at the beginning of the pandemic to modulate the severe inflammatory reaction observed in these patients [ [39] , [40] , [41] ]. These medications are known to prolong the QT segment and facilitate MACE.…”

Effects of evidence-based clinical practice guidelines for COVID-19 in health care quality improvements. A third systematic review.

“…We incorporated 15 randomized controlled trials examining EB-CPGs on COVID-19 (Barratt-Due et al, 2021;Ben Abdallah et al, 2023;Chen et al, 2023;Engelen et al, 2022;Gold et al, 2021;Gyselinck et al, 2022;Hamidi-Alamdari et al, 2021;Liesenborghs et al, 2021;Montejano et al, 2023;Rahman et al, 2022;Rauch et al, 2021;Sadeghi et al, 2023;Scholz et al, 2023;Suppan et al, 2020;Zurita-Cruz et al, 2022). Supplement N°3 contains supplementary information following screening and assessment of the complete text (Ramírez-Morera et al, 2023).…”

“…Supplement N°5 displays the guidelines that were evaluated in the included articles (Ramírez-Morera et al, 2023). Regarding the seriousness of COVID-19, one study was conducted in people with lower intensity COVID-19 cases (Gold et al, 2021), while ten studies focused on cases of moderate severity (Barratt-Due et al, 2021;Ben Abdallah et al, 2023;Chen et al, 2023;Engelen et al, 2022;Gyselinck et al, 2022;Hamidi-Alamdari et al, 2021;Liesenborghs et al, 2021;Rahman et al, 2022;Suppan et al, 2020, Zurita-Cruz et al, 2022. Furthermore, four studies specifically addressed individuals with more severe clinical conditions (Montejano et al, 2023;Sadeghi et al, 2023;Rauch et al, 2021;Scholz et al, 2023).…”

“…An investigation evaluated EB-CPG for its application in an outpatient setting (Gold et al, 2021), while 14 studies focused on its implementation within hospital environments (Barratt-Due et al, 2021;Ben Abdallah et al, 2023;Engelen et al, 2022;Gyselinck et al, 2022;Liesenborghs et al, 2021;Montejano et al, 2023;Rahman et al, 2022;Rauch et al, 2021;Sadeghi et al, 2023;Scholz et al, 2023;Suppan et al, 2020;Zurita-Cruz et al, 2022).…”

Care for adults with COVID ‐19: living guidelines from the National COVID ‐19 Clinical Evidence Taskforce

“…Recommendations against several other treatments have subsequently been made, primarily on the basis of the findings of the RECOVERY trial: convalescent plasma (fifteen studies, 16 122 participants 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ), lopinavir/ritonavir (nine studies, 9389 participants 20 , 68 , 78 , 95 , 96 , 97 , 98 , 99 , 100 ), colchicine (eight studies, 17 782 participants 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ), azithromycin (eight studies, 10 728 participants 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 ), and aspirin (one study, 14 892 participants 117 ). The recommendation against interferon β‐1a was primarily based on the findings of the SOLIDARITY trial (four studies, 4646 participants 13 , 32 , 118 , 119 ); that against ivermectin was based on the findings of nineteen studies (3869 participants…”