A Multicentre Open-label Two-arm Randomised Superiority Clinical Trial of Azithromycin Versus Usual Care In Ambulatory COVID19 (ATOMIC2)

NCT04381962 | Completed Phase 3 DMC

• 4 other identifiers: ATOMIC22020-001740-2628289220/HRA/2105
• Study Type: interventional
• Target: 298
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

COVID-19

Keywords

SARS-CoV-2; Coronavirus; COVID-19; Azithromycin; Respiratory failure; Mortality; Trial

Outcome Measures

Primary Outcomes (1)

• Proportion progressing to respiratory failure or death (all clinically-diagnosed participants)

  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.

  Determined at day 28 from randomisation.

Secondary Outcomes (6)

• 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.

Other Outcomes (1)

• Mechanistic analysis of blood and nasal biomarkers if available

  Samples to be collected prospectively at baseline and again if patient admitted, to be taken as soon as possible and within 72 hours of admission if possible.

Study Arms (2)

Azithromycin

EXPERIMENTAL

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.

Drug: Azithromycin Capsule

Usual standard care

NO INTERVENTION

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.

Interventions

Azithromycin Capsule DRUG

Azithromycin 500 mg OD PO 14 days

Azithromycin

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead
• Pfizer: collaborator

Study Sites (5)

Horton General Hospital

Banbury, Oxfordshire, OX3 9DU, United Kingdom

Location

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Ninewells Hospital

Dundee, Scotland, DD2 1SG, United Kingdom

Location

Birmingham City Hospital

Birmingham, B18 7QH, United Kingdom

Location

Sandwell General Hospital

West Bromwich, B71 4HJ, United Kingdom

Location

Related Publications (2)

• Hinks TSC, Barber VS, Black J, Dutton SJ, Jabeen M, Melhorn J, Rahman NM, Richards D, Lasserson D, Pavord ID, Bafadhel M. A multi-centre open-label two-arm randomised superiority clinical trial of azithromycin versus usual care in ambulatory COVID-19: study protocol for the ATOMIC2 trial. Trials. 2020 Aug 17;21(1):718. doi: 10.1186/s13063-020-04593-8.

  PMID: 32807209 BACKGROUND

• Hinks TSC, Cureton L, Knight R, Wang A, Cane JL, Barber VS, Black J, Dutton SJ, Melhorn J, Jabeen M, Moss P, Garlapati R, Baron T, Johnson G, Cantle F, Clarke D, Elkhodair S, Underwood J, Lasserson D, Pavord ID, Morgan S, Richards D. Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial. Lancet Respir Med. 2021 Oct;9(10):1130-1140. doi: 10.1016/S2213-2600(21)00263-0. Epub 2021 Jul 9.

  PMID: 34252378 DERIVED

Related Links

• ATOMIC2 homepage

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Respiratory Insufficiency

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Paul Little, MD PhD

  University of Southampton

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, Two-arm, Randomised Superiority Trial

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: May 11, 2020
• Study Start: June 3, 2020
• Primary Completion: January 29, 2021
• Study Completion: April 20, 2021
• Last Updated: May 6, 2021

Record last verified: 2020-05

Locations

GB (5)