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

University of Oxford

Status and phase: Completed; Phase 3

Conditions: COVID-19

Treatments: Drug: Azithromycin Capsule

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04381962

2020-001740-26 (EudraCT Number)

ATOMIC2

282892 (Other Identifier)

20/HRA/2105 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Intervention: Azithromycin 500 mg 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.

Comparator: 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.

Enrollment: 298 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

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-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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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298 participants in 2 patient groups

Azithromycin

Experimental group

Description:

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.

Treatment:

Drug: Azithromycin Capsule

Usual standard care

No Intervention group

Description:

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.