Publication 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
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|
500 mg orally once daily for 14 days
Standard care ( / )
Definition of Standard care: 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.
295 participants (n1=147 / n2= 148)
|Characteristics of participants|
Mean age : 45.9
Severity : Mild: n=2 / Moderate: n=0/ Severe: n=0 Critical: n=0
|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
Yes. In English
|Risk of bias
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
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.