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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Dr
Aisha
Anjum
-
Ukremap-cap@icnarc.org
More information about this study, what is involved and how to take part can be found on the study website.
COVID-19 (SARS-CoV-2 infection), influenza and pneumonia
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of April 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.
Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.
This study was designed by clinicians who cared for patients and conducted research during the 2009 H1N1 pandemic. Planning for this study started in 2011. For the past several years, the study has been recruiting patients with severe community-acquired pneumonia in the inter-pandemic period. It was designed to adapt to an acute pandemic need: that time has come. The aim of this study is to generate evidence that can be used to reduce mortality (death), ICU resource use and morbidity (illness) in patients who are severely ill from community-acquired pneumonia and/or COVID-19.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
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)
You can take part if:
You may not be able to take part if:
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 days1.2. Resident of a nursing home or long term care facility2. 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 treatment3. 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 treatment2. Admission to hospital over 14 days ago with acute COVID illness3. Expected to be discharged from hospital today or tomorrow4. 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 illness2. >24 h have elapsed since becoming eligible for this domain3. Known hypersensitivity to all of the study drugs in the site randomization schedule4. A specific antibiotic choice is indicated5. The treating clinician believes that participation in the domain would not be in the best interests of the patient6. 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 pneumonia2. 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 h3. 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 admission2. 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 admission3. 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 drug4. In areas where MERS-CoV infection is endemic, laboratory-confirmed MERS-CoV infection5. The treating clinician believes that participation in the domain would not be in the best interests of the patient6. Known hypersensitivity to an agent specified as an intervention in this domain7. Receiving an agent that is specified as an intervention in this domain as a usual medication prior to this hospitalization will exclude a patient from receiving that agent8. Known HIV infection will exclude a patient from receiving lopinavir/ritonavir9. Known or suspected pregnancy will result in exclusion from any intervention that includes lopinavir/ritonavir or hydroxychloroquine10. Receiving amiodarone as a usual medication prior to this hospitalization or any administration of amiodarone within the 72 h prior to assessment of eligibility will exclude a patient from receiving lopinavir/ritonavir11. High clinical risk of sustained ventricular dysrhythmia will exclude a patient from receiving hydroxychloroquine
Immune modulation domain:1.>24 h have elapsed since ICU admission2. Has already received any dose of one or more of any form of interferon, anakinra, tocilizumab, or sarilumab during this hospitalization or is on long-term therapy with any of these agents prior to this hospital admission3. Known condition or treatment resulting in ongoing immune suppression including neutropenia prior to this hospitalization4. Has been randomized in a trial evaluating an immune modulation agent for proven or suspected COVID-19 infection, where the protocol of that trial requires ongoing administration of study drug5. The treating clinician believes that participation in the domain would not be in the best interests of the patient
Immunoglobulin domain:1. Known hypersensitivity to an agent specified as an intervention in this domain will exclude a patient from receiving that agent2. Known previous history of transfusion-related acute lung injury will exclude a patient from receiving convalescent plasma3. Known objection to receiving plasma products will exclude a patient from receiving any plasma components
Therapeutic anticoagulation domain:1. >48 h have elapsed since ICU admission2. Clinical or laboratory bleeding risk or both that is sufficient to contraindicate therapeutic anticoagulation, including intention to continue or commence dual antiplatelet therapy3. Therapeutic anticoagulation is already present due to prior administration of any anticoagulant agent that is known or likely to still be active or a clinical decision has been made to commence therapeutic anticoagulation4. Enrolment in a trial evaluating anticoagulation for proven or suspected COVID-19 infection, where the protocol of that trial requires continuation of the treatment assignment specified in that trial5. Known or suspected previous adverse reaction to UFH or LMWH including heparin-induced thrombocytopenia (HIT)6. The treating clinician believes that participation in the domain would not be in the best interests of the patient
Updated anticoagulation domain:1. >48 h since ICU admission 2. Clinical indication to commence or continue therapeutic dose anticoagulation (not as part of REMAP-CAP therapeutic anticoagulation group) 3. Intention to continue or commence dual antiplatelet therapy4. Enrolment in a trial evaluating anticoagulation for proven or suspected COVID-19 infection, where the protocol of that trial requires continuation of the treatment assignment specified in that trial 5. Known or suspected previous adverse reaction to UFH or LMWH including heparin induced thrombocytopenia (HIT). 6. The treating clinician believes that participation in the domain would not be in the best interests of the patient 7. If prior therapeutic anticoagulation, the clinical or laboratory bleeding risk, or both, is sufficient to contraindicate continuation of therapeutic dose anticoagulation with heparin 8. If no prior therapeutic anticoagulation, the clinical or laboratory bleeding risk, or both, is sufficient to contraindicate intermediate dose thromboprophylaxis 9. If no prior therapeutic anticoagulation, and is receiving non-heparin anticoagulation medication (such as a direct acting oral anticoagulant) and the treating clinician believes that cessation and substitution with conventional low-dose thromboprophylaxis is either inappropriate or not possible
Antiplatelet domain:1. >48 h since ICU admission 2. Clinical or laboratory bleeding risk or both that is sufficient to contraindicate therapeutic anticoagulation, including intention to continue or commence dual anti-platelet therapy 3. Already receiving antiplatelet treatment or NSAID, or a clinical decision has been made to start antiplatelet or NSAID therapy 4. Enrolment in a trial evaluating anticoagulation or antiplatelet therapy for proven or suspected COVID-19 infection, where the protocol of that trial requires continuation of the treatment assignment specified in that trial 5. Aged >75 years 6. Patients receiving prior therapeutic anticoagulation 7. Creatinine clearance of <30 ml/min or receiving renal replacement therapy or ECMO8. Known hypersensitivity 9. The treating clinician believes that participation in the domain would not be in the best interests of the patient 10. P2Y12 Intervention specific exclusion11. Known or suspected to be pregnant
Simvastatin Domain:1. >48 h since ICU admission 2. Known severe liver disease 3. Known hypersensitivity to simvastatin 4. Creatinine more than 200 µmol/L (2.26 mg/dL) and not receiving renal replacement therapy 5. Current treatment with medicine that cannot be co-administered with simvastatin 6. Current treatment with any statin or treating clinician intends to commence treatment with any statin 7. Pregnant or breastfeeding. 8. The treating clinician believes that participation in the domain would not be in the best interests of the patient Vitamin C domain:1. >24 h since ICU admission 2. Patient has received any intravenous vitamin C during this hospitalisation (unless incorporated into parenteral nutrition) 3. Any of the following contraindications to vitamin C therapy:3.1. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency 3.2. Known allergy to vitamin C 3.3. Known history of symptomatic kidney stones within the past year 4. Has been randomised to a trial evaluating vitamin C, where the protocol of the trial requires ongoing administration of the study drug 5. The treating clinician believes that participation in the domain would not be in the best interests of the patient ACE2 RAS domain:1. >48 h since ICU admission in severe state or >96 h in moderate state 2. Patient is already receiving, or a clinical decision has been made to commence, an ACEi, ARB, direct renin inhibitor, angiotensin-receptor-neprilysin inhibitor, or chemokine receptor modulator 3. Long-term therapy prior to this hospital admission with one or more of ACEi, ARB, direct renin inhibitor, angiotensin-receptor-neprilysin inhibitor, or chemokine receptor modulator 4. Known hypersensitivity to ACEi or ARB, including angioedema 5. Treating clinician believes that administration of ACEi or ARB is inappropriate because of risk for: 5.1. Clinically relevant hypotension or escalation of vasopressor requirements5.2. Hyperkalemia6. Known severe renal artery stenosis 7. Patient is known or suspected to be pregnant or breastfeeding 8. Renal impairment with creatinine clearance < 30 ml/min or receiving renal replacement therapy 9. Enrollment in another trial evaluating ACEi, ARB, or other RAS modulator, or any targeted chemokine receptor modulation for proven or suspected COVID-19 infection, where the protocol of that trial requires continuation of the treatment assignment specified in that trial 10. If the domain is available at this site in the Moderate State and the patient is being assessed in the Severe state, prior assessment for this domain in the Moderate State 11. The treating clinician believes that participation in the domain would not be in the best interests of the patient 12. ARB + DMX-200 specific exclusions13. Known severe liver disease or an alanine aminotransferase or an aspartate aminotransferase that is more than 5 times the upper limit of normal 14. Known viral hepatitis 15. Hypersensitivity to repagermanium
Previous participant exclusion criteria: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 one or more 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
Patients will be deemed eligible for each treatment domain if they don't meet any of the following domain-specific exclusion criteria
Antibiotic domain:1. Received more than 48 h of intravenous antibiotic treatment for this index illness 2. More than 24 hours 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 indicated5. The treating clinician believes that participation in the domain would not be in the best interests of the patient
Macrolide duration domain (if randomised to a beta-lactam plus macrolide intervention within the antibiotic domain):1. 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 more than 24 hours 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 hours3. The treating clinician believes that participation in the domain would not be in the best interests of the patient
Antiviral domain:1. More than 24 hours have elapsed since ICU admission2. Patient has already received more than 36 hours of treatment with any non-trial prescribed systemic antiviral medication intended to be active against COVID-19 during this hospital admission3. Patient 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 drug4. In areas where MERS-CoV infection is endemic, the patient has laboratory-confirmed MERS-CoV infection5. The treating clinician believes that participation in the domain would not be in the best interests of the patient6. Known hypersensitivity to an agent specified as an intervention in this domain will exclude a patient from receiving that agent7. Receiving an agent that is specified as an intervention in this domain as a usual medication prior to this hospitalization will exclude a patient from receiving that agent8. Known HIV infection will exclude a patient from receiving lopinavir/ritonavir9. Known or suspected pregnancy will result in exclusion from any intervention that includes lopinavir/ritonavir or hydroxychloroquine10. Receiving amiodarone as a usual medication prior to this hospitalization or any administration of amiodarone within the 72 hours prior to assessment of eligibility will exclude a patient from receiving lopinavir/ritonavir11. High clinical risk of sustained ventricular dysrhythmia will exclude a patient from receiving hydroxychloroquine
Immune modulation domain:1. More than 24 h have elapsed since ICU admission2. Patient has already received any dose of one or more of any form of interferon, anakinra, tocilizumab, or sarilumab during this hospitalization or is on long-term therapy with any of these agents prior to this hospital admission3. Known condition or treatment resulting in ongoing immune suppression including neutropenia prior to this hospitalization4. Patient has been randomized in a trial evaluating an immune modulation agent for proven or suspected COVID-19 infection, where the protocol of that trial requires ongoing administration of study drug5. The treating clinician believes that participation in the domain would not be in the best interests of the patient
Immunoglobulin domain:1. Known hypersensitivity to an agent specified as an intervention in this domain will exclude a patient from receiving that agent2. Known previous history of transfusion-related acute lung injury will exclude a patient from receiving convalescent plasma3. Known objection to receiving plasma products will exclude a patient from receiving any plasma components
Therapeutic anticoagulation domain:1. More than 48 hours have elapsed since ICU admission2. Clinical or laboratory bleeding risk or both that is sufficient to contraindicate therapeutic anticoagulation, including intention to continue or commence dual antiplatelet therapy3. Therapeutic anticoagulation is already present due to prior administration of any anticoagulant agent that is known or likely to still be active or a clinical decision has been made to commence therapeutic anticoagulation4. Enrolment in a trial evaluating anticoagulation for proven or suspected COVID-19 infection, where the protocol of that trial requires continuation of the treatment assignment specified in that trial5. Known or suspected previous adverse reaction to UFH or LMWH including heparin-induced thrombocytopenia (HIT)6. The treating clinician believes that participation in the domain would not be in the best interests of the patient
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Dr
Aisha
Anjum
-
Ukremap-cap@icnarc.org
More information about this study, what is involved and how to take part can be found on the study website.
The study is sponsored by University Medical Center Utrecht and funded by European Commission.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Or CPMS 38197
You can print or share the study information with your GP/healthcare provider or contact the research team directly.
