Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (REMAP-CAP)
Community-acquired Pneumonia, Influenza, COVID-19
About this trial
This is an interventional treatment trial for Community-acquired Pneumonia, Influenza, COVID-19 focused on measuring Pneumonia, Lung Diseases, Respiratory Tract Diseases, Respiratory Tract Infections, Anti-Bacterial Agents, Moxifloxacin, Levofloxacin, Antibiotics, Hydrocortisone, Anti-Infective Agents, Ceftriaxone, Piperacillin-tazobactam, Ceftaroline, Amoxicillin-clavulanate, Oseltamivir, COVID-19, Influenza, Intensive care, Critical care, SARS-CoV-2, Vitamin C, Therapeutic Anticoagulation, Statin, Invasive Mechanical Ventilation, Convalescent plasma, Eritoran, Apremilast, DMX-200, Ivermectin
Eligibility Criteria
REMAP-CAP PLATFORM INCLUSION CRITERIA:
Adult patient admitted to an ICU for severe CAP within 48 hours of hospital admission with:
- symptoms or signs or both that are consistent with lower respiratory tract infection AND
- Radiological evidence of new onset consolidation (in patients with pre-existing radiological changes, evidence of new infiltrate)
Up to 48 hours after ICU admission, receiving organ support with one or more of:
- Non-invasive or Invasive ventilatory support;
- Receiving infusion of vasopressor or inotropes or both
PLATFORM EXCLUSION CRITERIA:
Healthcare-associated pneumonia:
- Prior to this illness, is known to have been an inpatient in any healthcare facility within the last 30 days
- Resident of a nursing home or long term care facility
- Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
- Previous participation in this REMAP within the last 90 days
REMAP-COVID PLATFORM INCLUSION CRITERIA
1. Adult patients (≥ 18 years) admitted to hospital with acute illness due to suspected or proven pandemic infection.
REMAP-COVID PLATFORM EXCLUSION CRITERIA
- Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
- Patient is expected to be discharged from hospital today or tomorrow
- More than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection.
- Previous participation in this REMAP within the last 90 days
DOMAIN-SPECIFIC ELIGIBLE CRITERIA:
Each domain may have additional eligibility criteria. Refer to the study website for more information (www.remapcap.org).
Sites / Locations
- University of FloridaRecruiting
- Augusta University
- University of Illinois HealthRecruiting
- Tulane Medical Center
- University of MichiganRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- Wake Forest Baptist Health
- The Ohio State University Wexner Medical CenterRecruiting
- Oregon Health and Science UniversityRecruiting
- University of Pittsburgh Medical CentreRecruiting
- Brown University - Rhode Island Hospital
- Canberra HospitalRecruiting
- Bankstown-Lidcombe HospitalRecruiting
- Blacktown HospitalRecruiting
- Campbelltown HospitalRecruiting
- Sutherland HospitalRecruiting
- Concord HospitalRecruiting
- Dubbo Base HospitalRecruiting
- Northern Beaches HospitalRecruiting
- Nepean HospitalRecruiting
- St. George HospitalRecruiting
- Liverpool HospitalRecruiting
- John Hunter HospitalRecruiting
- Orange Health Service
- St Vincent's Hospital SydneyRecruiting
- Prince of Wales HospitalRecruiting
- Royal Prince Alfred Hospital
- Royal North Shore HospitalRecruiting
- Wollongong HospitalRecruiting
- Wagga Wagga Base Hospital
- Westmead HospitalRecruiting
- Royal Darwin Hospital,
- Sunshine Coast University Hospital
- The Prince Charles HospitalRecruiting
- Mater Hospital BrisbaneRecruiting
- Princess Alexandra HospitalRecruiting
- Caboolture HospitalRecruiting
- Queen Elizabeth II Jubilee HospitalRecruiting
- Logan Hospital
- Redcliffe Hospital
- Rockhampton Hospital
- Gold Coast University HospitalRecruiting
- Toowoomba HospitalRecruiting
- Townsville HospitalRecruiting
- Royal Adelaide HospitalRecruiting
- The Queen Elizabeth HospitalRecruiting
- Lyell McEwin HospitalRecruiting
- Flinders Medical CentreRecruiting
- Launceston HospitalRecruiting
- Ballarat Base HospitalRecruiting
- Bendigo HospitalRecruiting
- Casey HospitalRecruiting
- Box Hill HospitalRecruiting
- Monash Medical CentreRecruiting
- Dandenong HospitalRecruiting
- Angliss Hospital
- Footscray HospitalRecruiting
- University Hosptial GeelongRecruiting
- The Alfred HospitalRecruiting
- Royal Melbourne HospitalRecruiting
- St Vincent's Hospital MelbourneRecruiting
- Maroondah HospitalRecruiting
- Sunshine HospitalRecruiting
- Werribee Mercy HospitalRecruiting
- St John of God Hospital MidlandRecruiting
- St John of God Hospital Murdoch
- Royal Perth HospitalRecruiting
- Sir Charles Gairdner HospitalRecruiting
- Fiona Stanley HospitalRecruiting
- St John of God SubiacoRecruiting
- AZ Sint-Jan
- CHU de Charleroi - Hôpital Civil Marie Curie
- Universitair Ziekenhuis Antwerp
- Universitair Ziekenhuis GentRecruiting
- Foothills Medical Centre
- Peter Lougheed Centre
- Rockyview General Hospital
- South Health Campus
- Royal Alexandra Hospital, AlbertaRecruiting
- University of Alberta HospitalRecruiting
- Surrey Memorial Hospital
- St Boniface General HospitalRecruiting
- Health Sciences Centre WinnipegRecruiting
- Grace HospitalRecruiting
- Dr. Everett Chalmers Regional Hospital
- The Moncton Hospital
- The Saint John General Hospital
- William Osler Health SystemRecruiting
- Brantford General HospitalRecruiting
- Hamilton general HospitalRecruiting
- Juravinski HospitalRecruiting
- St. Joseph's Healthcare HamiltonRecruiting
- Kingston Health Sciences Centre
- Grand River HospitalRecruiting
- St Mary's General HospitalRecruiting
- The Ottawa HospitalRecruiting
- Niagara HealthRecruiting
- Thunder Bay General Hospital
- Sunnybrook Health Sciences CentreRecruiting
- St. Michael's Hospital Unity Health TorontoRecruiting
- Mount Sinai HospitalRecruiting
- Toronto General HospitalRecruiting
- Toronto Western HospitalRecruiting
- St Joseph's Health Centre
- CIUSS Chaudieres-Appalaches (Levis)
- Hospital Maisonneuve-Rosemont
- Hôpital Fleury
- Centre Hospitalier de l'Universite de MontrealRecruiting
- McGill University Health CentreRecruiting
- Hopital du Sacre-Coeur de MontrealRecruiting
- CHU de Québec - Université LavalRecruiting
- IUCPQ-ULRecruiting
- Centre Hospitalier de l'Université de SherbrookeRecruiting
- Regina General HospitalRecruiting
- Universidad de La SabanaRecruiting
- General County Hospital PožegaRecruiting
- University Hospital Centre ZagrebRecruiting
- University Hospital for Infectious DiseasesRecruiting
- Charité - Universitätsmedizin Berlin - Infektiologie und Pneumologie
- Charité - Universitätsmedizin Berlin - Nephrologie
- Vivantes Klinikum Neukölln
- Universitätsklinikum Köln
- Universitätsklinikum Frankfurt
- University Medical Center Hamburg-Eppendorf (UKE)
- Medizinische Hochschule Hannover
- Universitätsklinikum JenaRecruiting
- Universitätsklinikum LeipzigRecruiting
- Universitäts Klinikum Tübingen
- Universitätsklinikum Würzburg
- Jósa András County HospitalRecruiting
- Csolnoky Ferenc Kórház - Veszprem County Hospital
- Almási Balogh Pál KórházRecruiting
- Apollo Main Hospital
- Apollo First Med HospitalRecruiting
- Apollo Vanagaram Hospital
- Apollo Speciality Hospital - OMRRecruiting
- Beaumont Hospital
- St. Vincent's University HospitalRecruiting
- University Hospital GalwayRecruiting
- St Marianna University School of MedicineRecruiting
- Yokohama City University HospitalRecruiting
- St. Marianna University Yokohama City Seibu HospitalRecruiting
- Saiseikai Kumamoto HospitalRecruiting
- Osaka City General HospitalRecruiting
- Nerima Hikarigaoka HospitalRecruiting
- Tokyo Metropolitan Bokutoh HospitalRecruiting
- Itabashi Chuo Medical CenterRecruiting
- Tokyo bay Urayasu-Ichikawa Medical CenterRecruiting
- Wakayama Medical UniversityRecruiting
- Chitwan Medical CollegeRecruiting
- Grande International HospitalRecruiting
- Hospital for Advanced Medicine and Surgery (HAMS)Recruiting
- Nepal MedicitiRecruiting
- Meander Medisch CentrumRecruiting
- Jeroen Bosch ZiekenhuisRecruiting
- Martini Hospital Groningen
- University Medical Center Groningen
- Leiden University Medical CenterRecruiting
- Canisius Wilhelmina ZiekenhuisRecruiting
- Radboud University Medical Center
- University Medical Center UtrechtRecruiting
- North Shore HospitalRecruiting
- CVICU, Auckland City HospitalRecruiting
- DCCM, Auckland City HospitalRecruiting
- Middlemore HospitalRecruiting
- Christchurch HospitalRecruiting
- Waikato HospitalRecruiting
- Taranaki Base HospitalRecruiting
- Rotorua HospitalRecruiting
- Tauranga HospitalRecruiting
- Wellington Regional HospitalRecruiting
- Whangarei HospitalRecruiting
- Ziauddin University Hospital Clifton CampusRecruiting
- Abbasi Shaheed HospitalRecruiting
- National Institute of Cardiovascular Diseases, KarachiRecruiting
- South City Hospital, KarachiRecruiting
- Ziauddin University North Nazimabad CampusRecruiting
- Centro Hospitalar do Medio TejoRecruiting
- Hospital Lusíadas Lisbon
- Clinical Hospital of Infectious and Tropical Diseases "Dr. Victor Babes"Recruiting
- King Abdulaziz Medical CityRecruiting
- Institut Hospital del Mar d'Investigacions Mèdiques
- Hospital Universitario Reina SofiaRecruiting
- Basildon HospitalRecruiting
- Basingstoke and North Hampshire Hospital
- Royal United Hospital, BathRecruiting
- Queen Elizabeth Hospital BirminghamRecruiting
- Birmingham City HospitalRecruiting
- Blackburn HospitalRecruiting
- Pilgrim's HospitalRecruiting
- Royal Bournemouth HospitalRecruiting
- Royal Sussex County HospitalRecruiting
- Southmead HospitalRecruiting
- Bristol Royal HospitalRecruiting
- Queen's Hospital, BurtonRecruiting
- Royal Papworth HospitalRecruiting
- Addenbrookes HospitalRecruiting
- Cumberland Royal InfirmaryRecruiting
- Ashford & St Peters Hospital Trust
- Chesterfield Royal HospitalRecruiting
- Countess of Chester HospitalRecruiting
- Colchester HospitalRecruiting
- University Hospital CoventryRecruiting
- North Manchester General HospitalRecruiting
- Darlington Memorial HospitalRecruiting
- Darent Valley HospitalRecruiting
- Russells Hall HospitalRecruiting
- University Hospital of North DurhamRecruiting
- Royal Devon and Exeter HospitalRecruiting
- Frimley Park HospitalRecruiting
- Queen Elizabeth HospitalRecruiting
- Medway Maritime HospitalRecruiting
- James Paget Kings Lynn HospitalRecruiting
- Royal Surrey County HospitalRecruiting
- Northwick Park HospitalRecruiting
- Hereford County HospitalRecruiting
- Barnet HospitalRecruiting
- Huddersfield Hospital
- King George HospitalRecruiting
- Ipswich HospitalRecruiting
- Kettering HospitalRecruiting
- Leeds Teaching Hospitals NHS TrustRecruiting
- Leicester Royal InfirmaryRecruiting
- Glenfield HospitalRecruiting
- Lincoln County HospitalRecruiting
- Liverpool Heart and Chest HospitalRecruiting
- Alder Hey HospitalRecruiting
- Royal Liverpool HospitalRecruiting
- University Hospital AintreeRecruiting
- Croydon University HospitalRecruiting
- Royal London HospitalRecruiting
- Whipps Cross HospitalRecruiting
- Newham HospitalRecruiting
- St Barts HosptialRecruiting
- North Middlesex HospitalRecruiting
- Royal Free HospitalRecruiting
- St Thomas' HospitalRecruiting
- Guy's HospitalRecruiting
- King's College HospitalRecruiting
- St George's HospitalRecruiting
- Royal Marsden HospitalRecruiting
- Ryal BromptonRecruiting
- Hammersmith HospitalRecruiting
- St Mary's HospitalRecruiting
- Charing Cross HospitalRecruiting
- Luton and Dunstable University Hospital
- Maidstone Hospital - Maidstone and Tunbridge Wells NHS TrustRecruiting
- Manchester Royal InfirmaryRecruiting
- The Christie HospitalRecruiting
- Wythenshawe HospitalRecruiting
- Queen Elizabeth Hospital, WoolwichRecruiting
- The James Cook University HospitalRecruiting
- Milton Keynes University HospitalRecruiting
- Royal Victoria Infirmary, NewcastleRecruiting
- Newcastle Freeman HospitalRecruiting
- Northampton General HospitalRecruiting
- Norfolk and Norwich University HospitalRecruiting
- City Hospital NottinghamRecruiting
- Queen's Medical Centre - Nottingham University Hospitals NHS TrustRecruiting
- George Eliot HospitalRecruiting
- Royal Oldham HospitalRecruiting
- Princess Royal University HospitalRecruiting
- John Radcliffe HospitalRecruiting
- Derriford HospitalRecruiting
- Poole Hospital NHS Foundation TrustRecruiting
- Queen Alexandra Hospital - Portsmouth Hospitals NHS TrustRecruiting
- Whiston Hospital
- Royal Preston HospitalRecruiting
- Royal Berkshire HospitalRecruiting
- Alexandra Hospital, RedditchRecruiting
- Queen's Hospital RomfordRecruiting
- Rotherham General HospitalRecruiting
- Salford Royal HospitalRecruiting
- Salisbury District HospitalRecruiting
- Royal Hallamshire HospitalRecruiting
- Northern General HospitalRecruiting
- Wexham Park HospitalRecruiting
- South Tyneside District HospitalRecruiting
- Southampton General HospitalRecruiting
- Stepping Hill HospitalRecruiting
- University Hospital of North TeesRecruiting
- Royal Stoke University HospitalRecruiting
- Sunderland HospitalRecruiting
- King's Mill HospitalRecruiting
- Great Western HospitalRecruiting
- Western General HospitalRecruiting
- Musgrove Park HospitalRecruiting
- Torbay and South Devon HospitalRecruiting
- Royal Cornwall HospitalRecruiting
- Tunbridge Wells Hospital - Maidstone and Tunbridge Wells NHS TrustRecruiting
- Harefield Hospital
- Watford General HospitalRecruiting
- Southend University HospitalRecruiting
- West Cumberland HospitalRecruiting
- Royal Albert Edward InfirmaryRecruiting
- Royal Hampshire HospitalRecruiting
- Arrow Park HospitalRecruiting
- New Cross HospitalRecruiting
- Worcester Royal HospitalRecruiting
- York HospitalRecruiting
- York HospitalRecruiting
- Antrim Area HospitalRecruiting
- Royal Victoria Hospital, BelfastRecruiting
- Mater HospitalRecruiting
- Belfast City HospitalRecruiting
- Altnagelvin HospitalRecruiting
- Aberdeen Royal InfirmaryRecruiting
- Ninewells HospitalRecruiting
- Royal Infirmary of EdinburghRecruiting
- Glasgow Royal InfirmaryRecruiting
- Queen Elizabeth University Hospital, GlasgowRecruiting
- Royal Alexandra Hospital, GlasgowRecruiting
- Neville Hall Hospital
- Glan Clywd HospitalRecruiting
- Princess of Wales HospitalRecruiting
- University Hospital of WalesRecruiting
- Glangwilli HospitalRecruiting
- Grange University HospitalRecruiting
- Royal Gwent Hospital
- Royal Glamorgan HospitalRecruiting
- Morriston HospitalRecruiting
- Wrexham Maelor HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Arm 16
Other
Other
Other
Other
Other
Other
Other
Other
Other
Other
Other
Other
Other
Other
Other
Other
Antibiotic Domain
Macrolide Duration Domain
Corticosteroid Domain
Influenza Antiviral Domain
COVID-19 Antiviral Domain
COVID-19 Immune Modulation Domain
Anticoagulation Domain
Immunoglobulin Domain
Vitamin C Domain
Simvastatin Domain
Antiplatelet Domain
Mechanical Ventilation Domain
COVID-19 Immune Modulation (2) Domain
ACE2 RAS Domain
Cysteamine Domain
Endothelial Domain
Patients with community-acquired pneumonia admitted to participating intensive care units and requiring empiric antibiotic therapy will be randomised one of five antibiotic interventions. Note: the ceftaroline + macrolide intervention has been closed to recruitment.
Patients with community-acquired pneumonia admitted to participating intensive care units who have been allocated to a beta-lactam antibiotic intervention in the Antibiotic Domain will be randomised to either a standard course or extended course of macrolide therapy
Patients with community acquired pneumonia (CAP) admitted to participating intensive care units will be randomised to a steroid use strategy. Note: this domain is now closed to patients with suspected or proven COVID-19. It remains open to patients with CAP without COVID-19.
Patients with community-acquired pneumonia admitted to participating intensive care units with microbiological testing confirmed influenza infection will be randomised to one of six interventions.
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to no ivermectin or ivermectin. Note: an earlier version of this domain evaluated lopinavir-ritonavir, hydroxychloroquine, and combination lopinavir-ritonavir and hydroxychloroquine against a 'no antiviral' control. This domain is now closed.
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five interventions. Note: this domain is now closed.
Patients admitted to participating intensive care units with suspected or microbiological testing confirmed COVID-19 will be randomised to an anticoagulation strategy. Note: A previous version of this domain evaluated local standard venous thromboprophylaxis against therapeutic dose anticoagulation.
Immunosuppressed patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive no immunoglobulin for COVID-19, or to receive high-titre convalescent plasma. Note: an earlier version of this domain was not restricted to immunosuppressed patients.
Patients admitted to participating hospitals with community-acquired pneumonia will be randomised to receive no vitamin C, or vitamin C. Note: this domain is now closed.
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no simvastatin, or simvastatin. Note: this domain is now closed.
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no antiplatelet, aspirin, or site-preferred P2Y12 inhibitor.
Patients with community-acquired pneumonia admitted to participating intensive care units who are intubated and receiving invasive mechanical ventilation will be randomised to protocolised mechanical ventilation strategy, or clinician-preferred mechanical ventilation strategy
Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive one of three interventions. Note: this domain is now closed.
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five renin-angiotensin system blockade strategies. Note: this domain is now closed.
Patients admitted to participating hospitals with severe community-acquired pneumonia, including patients with suspected or proven influenza or COVID-19, will be randomised to receive no cysteamine, or cysteamine.
Patients admitted to participating hospitals with severe community-acquired pneumonia, including patients with suspected or proven influenza or COVID-19, will be randomised to receive no endothelial modulator or enteral imatinib.