A randomised trial of treatments to prevent death in patients hospitalised with pneumonia

Phase 3

• Conditions: Severe Acute Respiratory Syndrome, COVID-19 (SARS coronavirus 2 [SARS-CoV-2] infection), Influenza A, Influenza B, Viral pneumonia syndrome, Community-acquired pneumonia, Bacterial pneumonia syndrome; Infections and Infestations

• Registration Number: ISRCTN50189673
• Lead Sponsor: niversity of Oxford

Brief Summary

2021 Results article in https://pubmed.ncbi.nlm.nih.gov/32678530/ Dexamethasone results (added 20/07/2020) 2020 Results article in https://doi.org/10.1016/S0140-6736(20)32013-4 Lopinavir–ritonavir results (added 06/10/2020) 2020 Results article in https://pubmed.ncbi.nlm.nih.gov/33031652/ Hydroxychloroquine results (added 09/11/2020) 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/33545096/ Azithromycin results (added 03/02/2021) 2021 Preprint results in https://doi.org/10.1101/2021.02.11.21249258 Tocilizumab results (added 12/02/2021) 2021 Preprint results in https://doi.org/10.1101/2021.03.09.21252736 Non-peer-reviewed convalescent plasma results (added 18/03/2021) 2021 Preprint results in https://doi.org/10.1101/2021.06.15.21258542 Non-peer-reviewed results for REGEN-COV (casirivimab and imdevimab) (added 23/07/2021) 2021 Preprint results in https://doi.org/10.1101/2021.06.08.21258132 Non-peer-reviewed results for aspirin (added 23/07/2021) 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/34000257/ Convalescent plasma results (added 23/07/2021) 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/33933206/ Tocilizumab results (added 23/07/2021) 2021 Preprint results in https://www.medrxiv.org/content/10.1101/2021.05.18.21257267v1 Non-peer-reviewed results for colchicine (added 21/10/2021) 2021 Results article in https://doi.org/10.1016/S2213-2600(21)00435-5 Colchicine results (added 21/10/2021) 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/34800427/ Aspirin results (added 24/11/2021) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/35151397/ Casirivimab and imdevimab results (added 14/02/2022) 2022 Preprint results in https://doi.org/10.1101/2022.03.02.22271623 Baricitinib results (added 28/03/2022) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/35908569/ Baricitinib results (added 02/08/2022) 2022 Preprint results in https://doi.org/10.1101/2022.09.23.22280285 Dimethyl fumarate results (added 28/12/2022) 2022 Preprint results in https://doi.org/10.1101/2022.12.16.22283578 Higher-dose dexamathasone results (added 28/12/2022) 2023 Results article in https://pubmed.ncbi.nlm.nih.gov/37060915/ Results for higher-dose corticosteroids in COVID-19 inpatients who were hypoxic but not receiving ventilatory support (added 17/04/2023) 2023 Results article in https://doi.org/10.1016/s2213-8587(23)00253-x Empagliflozin results (added 23/10/2023) 2024 Results article in https://pubmed.ncbi.nlm.nih.gov/38272046/ Immunomodulatory therapy results (added 30/01/2024) 2024 Results article in https://pubmed.ncbi.nlm.nih.gov/38296965/ Dimethyl fumarate results (added 09/02/2024) Results article in https://pubmed.ncbi.nlm.nih.gov/38951929/ RECOVERY baseline characteristics and outcomes compared with a reference popluation (added 02/07/2024)

Detailed Description

Not available

Study Timeline

• Study Start: 2020-04-02
• Last Update Posted: 15 July 2024
• Study Completion: 2036-06-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 50000

Inclusion Criteria

Current inclusion criteria as of 04/12/2023:

Patients are eligible for the study if all of the following are true:

(i)Hospitalised
(ii)Pneumonia syndrome
In general, pneumonia should be suspected when a patient presents with:
a)typical symptoms of a new respiratory tract infection (e.g. influenza-like illness with fever and muscle pain, or respiratory illness with cough and shortness of breath); and
b)objective evidence of acute lung disease (e.g. consolidation or ground-glass shadowing on X-ray or CT, hypoxia, or compatible clinical examination); and
c)alternative causes have been considered unlikely or excluded (e.g. heart failure).
However, the diagnosis remains a clinical one based on the opinion of the managing doctor (the above criteria are just a guide).
(iii)One of the following diagnoses:
a)Confirmed SARS-CoV-2 infection (including patients with influenza co-infection)
b)Confirmed influenza A or B infection (including patients with SARS-CoV-2 co-infection)
c)Community-acquired pneumonia with planned antibiotic treatment (excluding patients with suspected or confirmed SARS-CoV-2, influenza, active pulmonary tuberculosis or Pneumocystis jirovecii pneumonia)
(iv)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

_____

Previous inclusion criteria as of 28/03/2022:

1. Hospitalised
2.Viral pneumonia syndrome. In general, viral pneumonia should be suspected when a patient presents with:
2.1. typical symptoms (e.g. influenza-like illness with fever and muscle pain, or respiratory illness with cough AND
2.2. compatible chest X-ray findings (consolidation or ground-glass shadowing) AND
2.3. alternative causes have been considered unlikely or excluded (e.g. heart failure, bacterial pneumonia).
However, the diagnosis remains a clinical one based on the opinion of the managing doctor.
3. SARS-CoV-2 infection (clinically suspected or laboratory-confirmed)
4. 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

_____

Previous inclusion criteria as of 07/05/2020:

1. Hospitalised
2. SARS-CoV-2 infection (clinically suspected or laboratory-confirmed)
3. 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

______

Previous inclusion criteria:

1. Aged at least 18 years
2. Hospitalised
3. SARS-CoV-2 infection

Exclusion Criteria

Current exclusion criteria as of 04/12/2023:

Participants will be excluded if the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms (see Protocol Appendix 2; section 8.2, Appendix 3; section 8.3 for children, and Appendix 4 for pregnant and breastfeeding women), or that the patient should definitely be receiving one of the active drug treatment arms then that arm will not be available for randomisation for that patient. For patients who lack capacity, an advanced directive or behaviour that clearly indicates that they would not wish to participate in the trial would be considered sufficient reason to exclude them from the trial.

_____

Previous exclusion criteria as of 07/05/2020:

Participants will be excluded if the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms (see Protocol Appendix 2; section 8.2 and Appendix 3; section 8.3 for children), or that the patient should definitely be receiving one of the active drug treatment arms then that arm will not be available for randomisation for that patient. For patients who lack capacity, an advanced directive or behaviour that clearly indicates that they would not wish to participate in the trial would be considered sufficient reason to exclude them from the trial.

______

Previous exclusion criteria:

1. Patients will be excluded if they have a 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
2. In addition, if the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms, then the patient will be excluded from randomisation to that arm

Study & Design

• Study Type: Interventional
• Study Design: Not specified