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
BACKGROUND: Azithromycin is an orally active synthetic macrolide antibiotic with a wide range of anti-bacterial, anti-inflammatory and antiviral properties. It is a safe, inexpensive, generic licenced drug available worldwide and manufactured to scale and is a potential candidate therapy for pandemic coronavirus disease 2019 (COVID-19). Azithromycin was widely used to treat severe SARS-CoV and MERS-CoV, but to date, no randomised data are available in any coronavirus infections. Other ongoing trials are exploring short courses of azithromycin either in early disease, within the first 7 days of symptoms, when azithromycin's antiviral properties may be important, or late in disease when anti-bacterial properties may reduce the risk of secondary bacterial infection. However, the molecule's anti-inflammatory properties, including suppression of pulmonary macrophage-derived pro-inflammatory cytokines such as interleukins-1β, -6, -8, and -18 and cytokines G-CSF and GM-CSF may provide a distinct therapeutic benefit if given in as a prolonged course during the period of progression from moderate to severe disease.
METHODS: ATOMIC2 is a phase II/III, multi-centre, prospective, open-label, two-arm randomised superiority clinical trial of azithromycin versus standard care for adults presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation. We will enrol adults, ≥ 18 years of age assessed in acute hospitals in the UK with clinical diagnosis of COVID-19 infection where management on an ambulatory care pathway is deemed appropriate. Participants will be randomised in a 1:1 ratio to usual care or to azithromycin 500 mg orally daily for 14 days with telephone follow-up at days 14 and 28. The primary objective is to compare the proportion with either death or respiratory failure requiring invasive or non-invasive mechanical ventilation over 28 days from randomisation. Secondary objectives include mortality/respiratory failure in those with a PCR-confirmed diagnosis; all-cause mortality; progression to pneumonia; progression to severe pneumonia; peak severity of illness and mechanistic analysis of blood and nasal biomarkers.
DISCUSSION: This trial will determine the clinical utility of azithromycin in patients with moderately severe, clinically diagnosed COVID-19 and could be rapidly applicable worldwide.
TRIAL REGISTRATION: ClinicalTrials.gov NCT04381962 . Registered on 11 May 2020. EudraCT identifier 2020-001740-26 . Opened for accrual on 29 May 2020.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Trials - 21(2020), 1 vom: 17. Aug., Seite 718 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hinks, Timothy S C [VerfasserIn] |
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| Links: |
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| Themen: |
83905-01-5 |
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| Anmerkungen: |
Date Completed 25.08.2020 Date Revised 27.03.2024 published: Electronic ClinicalTrials.gov: NCT04381962 Citation Status MEDLINE |
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| doi: |
10.1186/s13063-020-04593-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313817723 |
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| 100 | 1 | |a Hinks, Timothy S C |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A multi-centre open-label two-arm randomised superiority clinical trial of azithromycin versus usual care in ambulatory COVID-19 |b study protocol for the ATOMIC2 trial |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 25.08.2020 | ||
| 500 | |a Date Revised 27.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04381962 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Azithromycin is an orally active synthetic macrolide antibiotic with a wide range of anti-bacterial, anti-inflammatory and antiviral properties. It is a safe, inexpensive, generic licenced drug available worldwide and manufactured to scale and is a potential candidate therapy for pandemic coronavirus disease 2019 (COVID-19). Azithromycin was widely used to treat severe SARS-CoV and MERS-CoV, but to date, no randomised data are available in any coronavirus infections. Other ongoing trials are exploring short courses of azithromycin either in early disease, within the first 7 days of symptoms, when azithromycin's antiviral properties may be important, or late in disease when anti-bacterial properties may reduce the risk of secondary bacterial infection. However, the molecule's anti-inflammatory properties, including suppression of pulmonary macrophage-derived pro-inflammatory cytokines such as interleukins-1β, -6, -8, and -18 and cytokines G-CSF and GM-CSF may provide a distinct therapeutic benefit if given in as a prolonged course during the period of progression from moderate to severe disease | ||
| 520 | |a METHODS: ATOMIC2 is a phase II/III, multi-centre, prospective, open-label, two-arm randomised superiority clinical trial of azithromycin versus standard care for adults presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation. We will enrol adults, ≥ 18 years of age assessed in acute hospitals in the UK with clinical diagnosis of COVID-19 infection where management on an ambulatory care pathway is deemed appropriate. Participants will be randomised in a 1:1 ratio to usual care or to azithromycin 500 mg orally daily for 14 days with telephone follow-up at days 14 and 28. The primary objective is to compare the proportion with either death or respiratory failure requiring invasive or non-invasive mechanical ventilation over 28 days from randomisation. Secondary objectives include mortality/respiratory failure in those with a PCR-confirmed diagnosis; all-cause mortality; progression to pneumonia; progression to severe pneumonia; peak severity of illness and mechanistic analysis of blood and nasal biomarkers | ||
| 520 | |a DISCUSSION: This trial will determine the clinical utility of azithromycin in patients with moderately severe, clinically diagnosed COVID-19 and could be rapidly applicable worldwide | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov NCT04381962 . Registered on 11 May 2020. EudraCT identifier 2020-001740-26 . Opened for accrual on 29 May 2020 | ||
| 650 | 4 | |a Clinical Trial Protocol | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Azithromycin | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Coronavirus | |
| 650 | 4 | |a Macrolide | |
| 650 | 4 | |a Mortality | |
| 650 | 4 | |a Randomised controlled trial | |
| 650 | 4 | |a Respiratory failure | |
| 650 | 4 | |a SAR-CoV-2 | |
| 650 | 4 | |a Trial | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Azithromycin |2 NLM | |
| 650 | 7 | |a 83905-01-5 |2 NLM | |
| 700 | 1 | |a Barber, Vicki S |e verfasserin |4 aut | |
| 700 | 1 | |a Black, Joanna |e verfasserin |4 aut | |
| 700 | 1 | |a Dutton, Susan J |e verfasserin |4 aut | |
| 700 | 1 | |a Jabeen, Maisha |e verfasserin |4 aut | |
| 700 | 1 | |a Melhorn, James |e verfasserin |4 aut | |
| 700 | 1 | |a Rahman, Najib M |e verfasserin |4 aut | |
| 700 | 1 | |a Richards, Duncan |e verfasserin |4 aut | |
| 700 | 1 | |a Lasserson, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Pavord, Ian D |e verfasserin |4 aut | |
| 700 | 1 | |a Bafadhel, Mona |e verfasserin |4 aut | |
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