COVID-19Phase 3ATOMIC2NCT04381962
A Multicentre Open-label Two-arm Randomised Superiority Clinical Trial of Azithromycin Versus Usual Care In Ambulatory COVID19 (ATOMIC2)
A Phase 3 study testing Azithromycin Capsule in people with COVID-19, run by University of Oxford at 5 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Azithromycin Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 298 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- 3 Jun 2020to 20 Apr 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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 locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
Horton General Hospital
Banbury, Oxfordshire, OX3 9DU
Birmingham City Hospital
Birmingham, B18 7QH
Ninewells Hospital
Dundee, Scotland, DD2 1SG
John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
Sandwell General Hospital
West Bromwich, B71 4HJ
About this study
Official title: A Multi-centre Open-label Two-arm Randomised Superiority Clinical Trial of Azithromycin Versus Usual Care In Ambulatory COVID-19 (ATOMIC2)
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.
Read the detailed 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.
- Conditions
- COVID-19
- Being tested
- Azithromycin Capsule
- Keywords
- SARS-CoV-2, Coronavirus, COVID-19, Azithromycin, Respiratory failure, Mortality, Trial
- Medical subject headings
- COVID-19, Coronavirus Infections, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin CapsuleDrug
Azithromycin 500 mg OD PO 14 days
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Determined at day 28 from randomisation.
Secondary outcomes (6)
Proportion progressing to respiratory failure or death (SARS-CoV-2 PCR positive)
Efficacy will be determined through differences in the proportion with either death or admission with respiratory failure requiring level 2 ventilatory support (NIV/CPAP/nasal high-flow) or level 3 (invasive mechanical ventilation) in the 28 days from randomisation using a retrospective analysis of COVID-19 oropharyngeal swabs for those who had one taken at time of randomisation.
Measured: Determined at day 28 from randomisation.
All cause mortality
Data on vital status (alive / dead, with date and presumed cause of death if appropriate)
Measured: Ascertain data at 28 days after randomisation.
Proportion progressing to pneumonia.
Progression to pneumonia as diagnosed by chest x-ray (or CT thorax), with compatible clinical findings, if no pneumonia is present at time of enrolment. To be diagnosed by a medically qualified doctor and data obtained from review of case-notes and relevant radiology.
Measured: Ascertain this information at time of pneumonia diagnosis, or at 28 days after randomisation (whichever is sooner)
Proportion progressing to severe pneumonia
Evolution of pneumonia, as diagnosed by chest x-ray or CT thorax, if pneumonia is present at time of enrolment. To be diagnosed by a medically qualified doctor and data obtained from review of case-notes and relevant radiology. Severe pneumonia is defined as BTS CURB-65 score of 3-5.
Measured: Ascertain this information at time of pneumonia diagnosis, or at 28 days after randomisation (whichever is sooner)
Peak severity of illness
The 9-point ordinal scoring system is described in the protocol reflects the severity of respiratory illness. The maximum severity score during the entire study period will be compared.
Measured: Ascertain from day 14 and day 28 telephone call and from retrospective ePR/medical notes data at 28 days after randomisation.
Safety and tolerability
Serious adverse events and concomitant medications. Record at enrolment, emergently during study period and proactively elicit at day 14 and at day 28.
Measured: Emergent data collection days 0-28 and elicit proactively at day 14 and day 28 post randomisation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2020
- Study start3 Jun 2020
- Primary completion29 Jan 2021
- Study completion20 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open label, Two-arm, Randomised Superiority Trial
- Masking
- None (open label)
- Enrolment
- 298 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Paul Little, MD PhD, Study chair, University of Southampton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04381962
- Sponsor's protocol ID
- ATOMIC2
- Other IDs
- 2020-001740-26, 282892, 20/HRA/2105
- Acronym
- ATOMIC2
- Status last verified
- May 2020
- First submitted
- 7 May 2020
- Last updated
- 6 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 32807209Hinks 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.
PubMed 34252378
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre Open-label Two-arm Randomised Superiority Clinical Trial of Azithromycin Versus Usual Care In Ambulatory COVID-19 (ATOMIC2)
- ClinicalTrials.gov ID
- NCT04381962
- Acronym / sponsor ID
- ATOMIC2 / ATOMIC2
- Conditions
- COVID-19
- Keywords
- SARS-CoV-2, Coronavirus, COVID-19, Azithromycin, Respiratory failure, Mortality, Trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 298 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 3 Jun 2020 (actual)
- Primary completion
- 29 Jan 2021 (actual)
- Study completion
- 20 Apr 2021 (actual)
- First posted
- 11 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open label, Two-arm, Randomised Superiority Trial
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Experimental | Drug: Azithromycin CapsuleAzithromycin 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. |
| 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycin CapsuleAzithromycin 500 mg OD PO 14 days | Drug | Azithromycin |
Primary outcome
Proportion progressing to respiratory failure or death (all clinically-diagnosed participants)
Time frame: 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.
6 secondary outcomes
Proportion progressing to respiratory failure or death (SARS-CoV-2 PCR positive)
Time frame: Determined at day 28 from randomisation.
All cause mortality
Time frame: Ascertain data at 28 days after randomisation.
Proportion progressing to pneumonia.
Time frame: Ascertain this information at time of pneumonia diagnosis, or at 28 days after randomisation (whichever is sooner)
Proportion progressing to severe pneumonia
Time frame: Ascertain this information at time of pneumonia diagnosis, or at 28 days after randomisation (whichever is sooner)
Peak severity of illness
Time frame: Ascertain from day 14 and day 28 telephone call and from retrospective ePR/medical notes data at 28 days after randomisation.
Safety and tolerability
Time frame: Emergent data collection days 0-28 and elicit proactively at day 14 and day 28 post randomisation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2021.
- Background: PubMed 32807209Hinks 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.
- Derived from this study: PubMed 34252378Hinks 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Little, MD PhD study chair
University of Southampton
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azithromycin Capsule in people with COVID-19, run by University of Oxford at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion progressing to respiratory failure or death (all clinically-diagnosed participants) (time frame: Determined at day 28 from randomisation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04381962, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.