Respiratory Medicine Unit and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Nuffield Department of Medicine Experimental Medicine, University of Oxford, Oxfordshire, OX3 9DU, UK.
Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Trials. 2020 Aug 17;21(1):718. doi: 10.1186/s13063-020-04593-8.
Azithromycin is an orally active synthetic macrolide antibiotic with a wide range of anti-bacterial, anti-inflammatory and antiviral properties. It is a safe, inexpensive, generic licenced drug available worldwide and manufactured to scale and is a potential candidate therapy for pandemic coronavirus disease 2019 (COVID-19). Azithromycin was widely used to treat severe SARS-CoV and MERS-CoV, but to date, no randomised data are available in any coronavirus infections. Other ongoing trials are exploring short courses of azithromycin either in early disease, within the first 7 days of symptoms, when azithromycin's antiviral properties may be important, or late in disease when anti-bacterial properties may reduce the risk of secondary bacterial infection. However, the molecule's anti-inflammatory properties, including suppression of pulmonary macrophage-derived pro-inflammatory cytokines such as interleukins-1β, -6, -8, and -18 and cytokines G-CSF and GM-CSF may provide a distinct therapeutic benefit if given in as a prolonged course during the period of progression from moderate to severe disease.
ATOMIC2 is a phase II/III, multi-centre, prospective, open-label, two-arm randomised superiority clinical trial of azithromycin versus standard care for adults presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation. We will enrol adults, ≥ 18 years of age assessed in acute hospitals in the UK with clinical diagnosis of COVID-19 infection where management on an ambulatory care pathway is deemed appropriate. Participants will be randomised in a 1:1 ratio to usual care or to azithromycin 500 mg orally daily for 14 days with telephone follow-up at days 14 and 28. The primary objective is to compare the proportion with either death or respiratory failure requiring invasive or non-invasive mechanical ventilation over 28 days from randomisation. Secondary objectives include mortality/respiratory failure in those with a PCR-confirmed diagnosis; all-cause mortality; progression to pneumonia; progression to severe pneumonia; peak severity of illness and mechanistic analysis of blood and nasal biomarkers.
This trial will determine the clinical utility of azithromycin in patients with moderately severe, clinically diagnosed COVID-19 and could be rapidly applicable worldwide.
ClinicalTrials.gov NCT04381962 . Registered on 11 May 2020. EudraCT identifier 2020-001740-26 . Opened for accrual on 29 May 2020.
阿奇霉素是一种具有广泛抗菌、抗炎和抗病毒特性的口服活性合成大环内酯类抗生素。它是一种安全、廉价、通用的许可药物，在全球范围内均可获得，并可按规模生产，是治疗 2019 年冠状病毒病（COVID-19）大流行的潜在候选药物。阿奇霉素曾广泛用于治疗严重的 SARS-CoV 和 MERS-CoV，但迄今为止，尚无任何冠状病毒感染的随机数据。其他正在进行的试验正在探索早期疾病（症状出现的前 7 天内）、阿奇霉素的抗病毒特性可能很重要时，或疾病晚期（当抗菌特性可能降低继发细菌感染的风险时）使用短疗程阿奇霉素。然而，如果在从中度疾病向重度疾病进展的过程中给予延长疗程，该分子的抗炎特性，包括抑制肺巨噬细胞衍生的促炎细胞因子，如白细胞介素-1β、-6、-8 和-18 以及细胞因子 G-CSF 和 GM-CSF，可能提供独特的治疗益处。
ATOMIC2 是一项 II/III 期、多中心、前瞻性、开放标签、双臂随机优效性临床试验，比较阿奇霉素与标准治疗对因 COVID-19 症状就诊但在初次就诊时未住院的成人的疗效。我们将招募年龄在 18 岁及以上的成年人，他们在英国急性医院接受临床诊断为 COVID-19 感染，且被认为适合在门诊护理途径上进行管理。参与者将以 1:1 的比例随机分配接受常规护理或阿奇霉素 500mg 口服，每日一次，共 14 天，并在第 14 天和第 28 天进行电话随访。主要终点是比较随机分组后 28 天内死亡或需要有创或无创机械通气的呼吸衰竭的比例。次要终点包括 PCR 确诊诊断的死亡率/呼吸衰竭；全因死亡率；进展为肺炎；进展为重症肺炎；疾病严重程度峰值和血液及鼻腔生物标志物的机制分析。
这项试验将确定阿奇霉素在中度严重、临床诊断为 COVID-19 的患者中的临床应用价值，并且可能在全球范围内迅速应用。
ClinicalTrials.gov NCT04381962。于 2020 年 5 月 11 日注册。EudraCT 标识符 2020-001740-26。2020 年 5 月 29 日开始入组。
