Covid-19 Living Data

Trial NCT04381962
Publication ATOMIC2 - Hinks T, Lancet Respir Med (2021) (published paper)
Dates: 2020-06-03 to 2021-01-29
Funding: Mixed (NIHR Oxford BRC, University of Oxford and Pfizer Inc)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / UK Follow-up duration (days): 28
Inclusion criteria	aged at least 18 years, assessed by the attending clinical team as appropriate for ambulatory (outpatient) management clincial diagnosis of highly-probably or confirmed COVID-19 infection with onset of first symptoms within the last 14 days no medical history that might put the patient at significant risk able to understand written English and able to give informed consent
Exclusion criteria	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-isomaltose insufficiency currently on macrolide antibiotic (Clarithromycin, Azithromycin, Erythromycin, Telithromycin, Spiramycin) Elevated cardiac troponin at initial assessment suggestive of significant myocarditis evidence of QTc prolongation: QTc>480ms Significant electrolyte disturbance (e.g. hypokalemia 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
Interventions
	Treatment Azithromycin 500 mg orally once daily for 14 days
	Control Standard care
Participants
	Randomized participants : Azithromycin=147 Standard care=148
	Characteristics of participants N= 295 Mean age : NR 152 males Severity : Mild: n= 293/ Asymptomatic: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register Proportion progressing to respiratory failure or death (all clinically-diagnosed participants) [ Time Frame: Determined at day 28 from randomisation.]
	In the report Proportion of participants with hospital admission or death from any cause within 28 days from randomisation
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication:
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. There were no differences between the article and the registry or protocol in population, procedures and interventions. The primary outcome in the pre-print article (proportion of participants with hospital admission or death from any cause) was changed on advice from the data safety monitoring committee and with ethical approval from the original primary outcome in the registry and protocols (proportion progressing to hospitalization with respiratory failure or death) due to lack of events at interim analysis. The sample size in the registry was recalculated in accordance WHO recommendations that a pilot phase with 100 patients would be sufficient to inform follow-on clinical research and reduced from 800 to 291. Some outcomes reported in the registry are not reported in the paper (mechanistic analysis of blood and nasal biomarkers). This study was updated on July 28th, 2021 with data from contact with authors and publication.