A Multi-centre Open-label Two-arm Randomised Superiority Clinical Trial of Azithromycin Versus Usual Care In Ambulatory COVID-19 (ATOMIC2)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 298
- 试验地点
- 5
- 主要终点
- Proportion progressing to respiratory failure or death (all clinically-diagnosed participants)
研究概览
简要总结
A multi-centre open-label two-arm randomised superiority clinical trial of two weeks of oral Azithromycin 500mg once daily versus usual care in adult patients presenting to secondary care with clinically-diagnosed COVID-19 but assessed as appropriate for initial ambulant (outpatient) management, in preventing progression to respiratory failure or death.
详细描述
Hypothesis: Use of Azithromycin 500 mg once daily for 14 days is effective in preventing and/or reducing the severity of lower respiratory illness of COVID-19 disease at 28 days.
Study design: Multi centre, prospective open label two-arm randomised superiority clinical trial of standard care and Azithromycin with standard care alone for those presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation.
Study setting: Patients being assessed by secondary care NHS hospitals in the UK.
Participants: Adults, ≥18 years of age assessed in an acute hospital with clinical diagnosis of COVID-19 infection and where medically it is decided not to admit the patient and for the patient to be managed on an ambulatory (outpatient) care pathway at their usual residence (home or care home).
Study schedule: Enrolment on day 0. Telephone follow up at day 14 day, and day 28. If admitted between randomisation and day 28, data will be collected until hospital discharge.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study. However, while the study is in progress, access to tabular results by allocated treatment allocation will not be available to the research team, patients, or members of the Steering Committee (unless the DSMC advises otherwise).
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or Female, aged at least 18 years
- •Assessed by the attending clinical team as appropriate for initial ambulatory (outpatient) management
- •A clinical diagnosis of highly-probable COVID-19 infection (diagnosis by the attending clinical team)
- •No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial
- •Able to understand written English (for the information and consent process) and be able to give informed consent
排除标准
- •Known hypersensitivity to any Macrolide including Azithromycin, Ketolide antibiotic, or the excipients including an allergy to soya or peanuts.
- •Known fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase-insufficiency
- •Currently on a Macrolide antibiotic (Clarithromycin, Azithromycin, Erythromycin, Telithromycin, Spiramycin)
- •On any SSRI (Selective Serotonin Reuptake Inhibitor)
- •Elevated cardiac troponin at initial assessment suggestive of significant myocarditis (if clinically the clinical team have felt it appropriate to check the patient's troponin levels)
- •Evidence of QTc prolongation: QTc>480ms
- •Significant electrolyte disturbance (e.g. hypokalaemia K+<3.5 mmol/L)
- •Clinically relevant bradycardia (P<50 bpm), non-sustained ventricular tachycardia or unstable severe cardiac insufficiency
- •Currently on hydroxychloroquine or chloroquine
研究组 & 干预措施
Azithromycin
Azithromycin 2x250mg capsules to be taken orally once daily for 14 days. The first dose will be within 4 hours of randomisation. This is in addition to standard care as per local hospital advice for those patients with suspected COVID who are not admitted: i.e. symptomatic relief with rest, as-required paracetamol (where appropriate) and advice to seek further medical attention if significant worsening of breathlessness.
干预措施: Azithromycin Capsule (Drug)
结局指标
主要结局
Proportion progressing to respiratory failure or death (all clinically-diagnosed participants)
时间窗: Determined at day 28 from randomisation.
Efficacy will be determined through differences in the proportion with either death or admission with respiratory failure requiring level 2 ventilation (NIV/CPAP/nasal high-flow) or level 3 (invasive mechanical ventilation) in the 28 days from randomisation.
次要结局
- Proportion progressing to respiratory failure or death (SARS-CoV-2 PCR positive)(Determined at day 28 from randomisation.)
- All cause mortality(Ascertain data at 28 days after randomisation.)
- Proportion progressing to pneumonia.(Ascertain this information at time of pneumonia diagnosis, or at 28 days after randomisation (whichever is sooner))
- Proportion progressing to severe pneumonia(Ascertain this information at time of pneumonia diagnosis, or at 28 days after randomisation (whichever is sooner))
- Peak severity of illness(Ascertain from day 14 and day 28 telephone call and from retrospective ePR/medical notes data at 28 days after randomisation.)
- Safety and tolerability(Emergent data collection days 0-28 and elicit proactively at day 14 and day 28 post randomisation.)