Severe Community Acquired Pneumonia MedDRA version: 20.1 Level: LLT Classification code 10010120 Term: Community acquired pneumonia System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Levofloxacin
Product Name: Levofloxacin 5mg/ml Solution for Infusion
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: LEVOFLOXACIN HEMIHYDRATE
CAS Number: CAS 138199-7
Conce
Sponsors
University Medical Center Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General REMAP-CAP Inclusion Criteria: 1. Adult patient admitted to an ICU for acute severe CAP within 48 hours of hospital admission with a. symptoms or signs or both that are consistent with lower respiratory tract infection (for example, acute onset of dyspnea, cough, pleuritic chest pain) AND b. Radiological evidence of new onset infiltrate of infective origin (in patients with pre-existing radiological changes, evidence of new infiltrate). 2. Up to 48 hours after ICU admission, receiving organ support with one or more of: a. Non-invasive or invasive ventilatory support; b. Receiving infusion of vasopressor or inotropes or both. DOMAIN LEVEL: Domain specific inclusion criteria Macrolide Domain: Patients are eligible for this domain only if they have been allocated a beta-lactam plus macrolide intervention within the Antibiotic Domain. Influenza Antiviral Domain: Influenza infection is confirmed by microbiological testing. Anticoagulation Domain: COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing. Microbiological testing for SARS-CoV-2 of upper or lower respiratory tract secretions or both has occurred or is intended to occur. Antiplatelet Domain: COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing. Microbiological testing for SARS-CoV-2 of upper or lower respiratory tract secretions or both has occurred or is intended to occur. Mechanical Ventilation Domain: Receiving invasive mechanical ventilation. The most recent PaO2:FiO2 ratio obtained within the preceding 6 hours is less than 200 mmHg. Treating clinician expects the patient to still require invasive mechanical ventilation tomorrow. Treating clinician regards Protocolized Mechanical Ventilation Strategy or their preferred mode as (equally) appropriate for this patient. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2000 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2000
Exclusion criteria
Exclusion criteria: General platform exclusion criteria (Core Protocol): 1. Healthcare-associated pneumonia: a) Prior to this, is known to have has been an inpatient in any healthcare facility within the last 30 days b) Resident of a nursing home or long-term care facility 2. 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 3. Previous participation in this REMAP within the last 90 days Exclusion criteria for the pandemic aspects of REMAP-CAP: 1. 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 2. Patient is expected to be discharged from hospital today or tomorrow 3. More than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection 4. Previous participation in this REMAP within the last 90 days. There are domain-specific exclusion criteria in the Antibiotic, macrolide duration, Influenza Antiviral Domain, Anticoagulation Domain, Mechanical Ventilation Domain, Antiplatelet Domain and Corticosteroid domain. These have not changed compared to previous submissions. Due to maximum number of characters, only the domain-specific and interaction-specific exclusions for the adjusted Influenza Antiviral domain and new Immune Modulation Influenza domain are mentioned below. Influenza Antiviral Domain: Patients will be excluded from this domain if they have any of the following: • If in the Moderate State, more than 96 hours has elapsed since hospital admission • If in the Severe State, more than 48 hours has elapsed since ICU admission, unless the patient has already been assigned a treatment in another domain in the Moderate State, in which case exclusion will occur if more than 48 hours has elapsed since commencement of sustained organ failure support in an ICU • Patient has already received two or more doses of oseltamivir or other neuraminidase inhibitors • Patient has already received one or more doses of baloxavir • Patient is already receiving, or a clinical decision has been made to commence, an antiviral active against influenza other than oseltamivir or baloxavir or both. • The treating clinician believes that participation in the domain would not be in the best interests of the patient Immune Modulation Influenza domain: Patients will be excluded from this domain if they have any of the following: • SARS-CoV-2 infection has been confirmed by microbiological testing • Known condition or treatment resulting in ongoing immune suppression including neutropenia prior to this hospitalization • A neutrophil count <1.0 x 109 / L • Confirmed or strongly-suspected active mycobacterial infection or invasive fungal infection • Patient has already received any dose of one or more of any form of tocilizumab or another IL-6 receptor antagonist (e.g. sarilumab), baricitinib or another JAK inhibitor (e.g. tofacitinib, ruxolitinib or upadacitinib) during this hospitalization or is on long-term therapy with any of these agents prior to this hospital admission. • The treating clinician believes that participation in the domain would not be in the best interests of the patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this REMAP is, for adult patients with severe CAP who are admitted to an ICU, to identify the effect of a range of interventions to improve outcome as defined by the occurrence of death during the index hospital admission censored 90 days (or 21 days in case of pandemic) from the date of enrolment. ;Secondary Objective: The secondary objectives are to determine, for adult patients with severe CAP who are admitted to an ICU, the effect of interventions on ICU mortality, ICU length of stay (LOS), hospital LOS, ventilator free days (VFDs) censored at 28 days, organ failure free days (OFFDs) censored at 28 days, other endpoints as indicated for specific domains, and, where feasible or specified in a DSA, survival at 6 months (in case of a pandemic, 90 days outcome will be a secondary objective), health related quality of life (HRQoL) assessed after 6 months using the EQ5D and disability assessed after 6 months using the World Health Organization Disability Assessment Schedule (WHODAS). ;Primary end point(s): The primary objective of this REMAP is, for adult patients with severe CAP who are admitted to an ICU, to identify the effect of a range of interventions to improve outcome as defined by all-cause mortality at 90 days (or at 21 days in case of a pandemic).;Timepoint(s) of evaluation of this end point: 90 Days from the date of enrolment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives are to determine, for adult patients with severe CAP who are admitted to an ICU, the effect of interventions on ICU mortality, ICU length of stay (LOS), hospital LOS, ventilator free days (VFDs) censored at 28 days, organ failure free days (OFFDs) censored at 28 days, other endpoints as indicated for specific domains, and, where feasible or specified in a DSA, survival at 6 months, health related quality of life (HRQoL) assessed after 6 months using the EQ5D and disability assessed after 6 months using the World Health Organization Disability Assessment Schedule (WHODAS). ;Timepoint(s) of evaluation of this end point: The secondary objectives are to determine, for adult patients with severe CAP who are admitted to an ICU, the effect of interventions on ICU mortality, ICU length of stay (LOS), hospital LOS, ventilator free days (VFDs) censored at 28 days, organ failure free days (OFFDs) censored at 28 days, other endpoints as indicated for specific domains, and, where feasible or specified in a DSA, survival at 6 months (in case of a pandemic, 90 days outcome will be a secondary objective), health related quality of life (HRQoL) assessed after 6 months using the EQ5D and disability assessed after 6 months using the World Health Organization Disability Assessment Schedule (WHODAS). | — |
Countries
Australia, Belgium, Canada, Croatia, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, New Zealand, Portugal, Romania, Slovenia, Spain, United Kingdom
Contacts
Public ContactJulius Centrum UMCU
University Medical Center Utrecht
Outcome results
None listed