An international platform trial for severely ill patients with community-acquired pneumonia or COVID-19
- Conditions
- COVID-19 (SARS-CoV-2 infection), influenza and pneumoniaInfections and InfestationsInfluenza and pneumonia
- Registration Number
- ISRCTN67000769
- Lead Sponsor
- niversity Medical Center Utrecht
- Brief Summary
2020 Protocol article in https://pubmed.ncbi.nlm.nih.gov/32267771/ protocol (added 16/07/2020) 2020 Results article in https://pubmed.ncbi.nlm.nih.gov/32876697/ results for hydrocortisone (added 03/09/2020) 2021 Preprint results in https://doi.org/10.1101/2021.01.07.21249390 results for tocilizumab and sarilumab in preprint (added 08/01/2021) 2021 Results article in https://doi.org/10.1056/NEJMoa2100433 results for tocilizumab and sarilumab (added 18/03/2021)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 4400
Current participant inclusion criteria as of 19/04/2021:
Non-pandemic participants:
1. Adult patient admitted to an ICU for severe CAP within 48 h of hospital admission with both of the following:
1.1. Symptoms or signs or both that are consistent with lower respiratory tract infection (for example, acute onset of dyspnea, cough, pleuritic chest pain)
1.2. Radiological evidence of new-onset consolidation (in-patients with pre-existing radiological changes, evidence of new infiltrate)
2. Requiring organ support with one or more of:
2.1. Non-invasive or invasive ventilatory support
2.2. Receiving infusion of vasopressor or inotropes or both
Pandemic participants:
1. Adult patient with confirmed or suspected pandemic infection
Domain-specific criteria:
Antiviral domain:
1. COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing
2. Microbiological testing for SARS-CoV-2 infection of upper or lower respiratory tract secretions or both has occurred or is intended to occur
Immune modulation domain:
1. COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing
2. Microbiological testing for SARS-CoV-2 infection of upper or lower respiratory tract secretions or both has occurred or is intended to occur
Immunoglobulin domain:
1. COVID-19 infection is confirmed by microbiological testing
Therapeutic anticoagulation domain:
1. COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing
2. Microbiological testing for SARS-CoV-2 infection of upper or lower respiratory tract secretions or both has occurred or is intended to occur
Updated anticoagulation domain:
1. COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing
2. Microbiological testing for SARS-CoV-2 infection of upper or lower respiratory tract secretions or both has occurred or is intended to occur
Antiplatelet domain:
1.COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing
2. Microbiological testing for SARS-CoV-2 infection of upper or lower respiratory tract secretions or both has occurred or is intended to occur
Simvastatin Domain:
1. COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing
2. Microbiological testing for SARS-CoV-2 infection of upper or lower respiratory tract secretions or both has occurred or is intended to occur
Vitamin C domain:
1. COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing
2. Microbiological testing for SARS-CoV-2 infection of upper or lower respiratory tract secretions or both has occurred or is intended to occur
ACE2 RAS domain:
1. COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological t
Current participant exclusion criteria as of 19/04/2021:
Non-pandemic participants:
1. Healthcare-associated pneumonia:
1.1 Prior to this illness, has been an in-patient in any healthcare facility within the last 30 days
1.2. Resident of a nursing home or long term care facility
2. Death is deemed imminent or inevitable during this hospital admission and >1 of the patient, substitute decision-maker, or attending physician are not committed to full active treatment
3. Previous participation in this REMAP within the last 90 days
Pandemic participants:
1. Death is deemed imminent or inevitable during the next 24 h and >1 of the patient, substitute decision-maker, or attending physician are not committed to full active treatment
2. Admission to hospital over 14 days ago with acute COVID illness
3. Expected to be discharged from hospital today or tomorrow
4. Previous participation in this REMAP within the last 90 days
Domain-specific criteria:
Antibiotic domain:
1. Received >48 h of intravenous antibiotic treatment for this index illness
2. >24 h have elapsed since becoming eligible for this domain
3. Known hypersensitivity to all of the study drugs in the site randomization schedule
4. A specific antibiotic choice is indicated
5. The treating clinician believes that participation in the domain would not be in the best interests of the patient
6. If randomised to a beta-lactam plus macrolide intervention within the antibiotic domain and the treating clinician believes that participation in the domain would not be in the best interests of the patient
Corticosteroid domain:
1. An indication to prescribe systemic corticosteroids for a reason other than community-acquired pneumonia (CAP) (or severe sepsis) such as chronic corticosteroid use before admission, acute severe asthma, or suspected or proven pneumocystis jiroveci pneumonia
2. Have received an immunomodulatory dose of systemic corticosteroid therapy for >24 h prior to the time of enrolment. An immunomodulatory dose is defined as >20 mg of hydrocortisone, >5 mg prednisone, >4 mg methylprednisolone or >0.8 mg dexamethasone per 24 h
3. The treating clinician believes that participation in the domain would not be in the best interests of the patient
Antiviral domain:
1. >24 h have elapsed since ICU admission
2. Has already received >36 h of treatment with any non-trial prescribed systemic antiviral medication intended to be active against COVID-19 during this hospital admission
3. Has been randomized in a trial evaluating an antiviral intended to be active against COVID-19, where the protocol of that trial requires ongoing administration of study drug
4. In areas where MERS-CoV infection is endemic, laboratory-confirmed MERS-CoV infection
5. The treating clinician believes that participation in the domain would not be in the best interests of the patient
6. Known hypersensitivity to an agent specified as an intervention in this domain
7. Receiving an agent that is specified as an int
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method