E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Community Acquired Pneumonia |
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E.1.1.1 | Medical condition in easily understood language |
Severe Pneumonia |
Vaikea keuhkokuume |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010120 |
E.1.2 | Term | Community acquired pneumonia |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 from the date of enrolment. The primary outcome in the pandemic domain is days alive and without intensive care at 21 days from enrollment.
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E.2.2 | Secondary objectives of the trial |
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). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
General REMAP-CAP Inclusion Criteria (including adaptations for the pandemic domain) 1. Adult patient admitted to an ICU for acute severe CAP 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
Additional inclusions for the COVID-19 immunomodulation domain: • COVID-19 infection is suspected by the treating clinician or has been confirmed by microbiological testing • Microbiological testing for SARS-CoV-2 infection of upper or lower respiratory tract secretions or both has occurred or is intended to occur
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E.4 | Principal exclusion criteria |
General REMAP-CAP Exclusion Criteria adapted for the pandemic domain: 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. Previous participation in this REMAP within the last 90 days
COVID-19 Immune Modulation domain: Patients will be excluded from this domain if they have any of the following: • More than 24 hours has elapsed since ICU admission • Patient has already received any dose of any form of interferon or anakinra, or is on long-term therapy with any of these agents prior to this hospital admission • Known condition or treatment resulting in ongoing immune suppression including neutropenia prior to this hospitalization • 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 drug • The treating clinician believes that participation in the domain would not be in the best interests of the patient
Patients may also be excluded from receiving one or more interventions within the domain for patient-specific reasons. In such cases, patients will be randomly allocated a remaining intervention from among those available at that site. Patients who are eligible for only a single intervention at a site (i.e. all other interventions are contraindicated) are not eligible for this domain. Patients in whom all interventions are contraindicated will be treated according to the current standard of care at the clinician’s discretion. • Known hypersensitivity to an agent specified as an intervention in this domain will exclude a patient from receiving that agent • 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 agent • Intention to prescribe systemic corticosteroids for any reason, other than participation in the Corticosteroid Domain of this platform, will result in exclusion from receiving IFN-β1a • Known hypersensitivity to proteins produced by E. coli will result in exclusion from receiving anakinra • Known or suspected pregnancy will result in exclusion from the anakinra and IFN-β1a interventions. It is normal clinical practice that women admitted who are in an age group in which pregnancy is possible will have a pregnancy test conducted. The results of such tests will be used to determine interpretation of this exclusion criteria.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome in the pandemic domain is days alive and without intensive care at 21 days from enrollment.
The primary outcome in the core trial is by all-cause mortality at 90 days |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
21/90 Days from the date of enrolment. |
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E.5.2 | 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 90-day mortality (as a secondary endpoint tan the pandemic domain), 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). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
28 days, 90 days, 6 months as listed above |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 20 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Croatia |
Czech Republic |
Denmark |
Finland |
Germany |
Greece |
Hungary |
Ireland |
Netherlands |
New Zealand |
Portugal |
Romania |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |