Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia

At a glance

What the study gets you

Access to the study treatment being tested

Type of study

Interventional (receives a drug or procedure)

Time in hospital

In-person visits at study sites — visit count not specified by the sponsor

Drug or intervention

Ceftriaxone (drug), Moxifloxacin or Levofloxacin (drug), Piperacillin-tazobactam (drug), Ceftaroline (drug) +58 more

How long the study runs

Study runs about 142 months (dates as stated)

About the drug or intervention

Ceftriaxone — drug: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice. · Moxifloxacin or Levofloxacin — drug: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice. · Piperacillin-tazobactam — drug: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice. · Ceftaroline — drug: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice. · Amoxicillin-clavulanate — drug: The duration and dose of empiric antibiotics will be determined by the treating clinician and local guidelines or practice. · Standard course macrolide — drug: Standard course of macrolide therapy, discontinued between study day 3 and the end of study day 5. · Extended course macrolide — drug: Extended course of macrolide therapy discontinued at the end of study day 14 or hospital discharge (whichever occurs first). · No systemic corticosteroid — other: Patients are not to receive any systemic corticosteroids, including hydrocortisone, to study day 28 or hospital discharge (whichever occurs first). · Fixed-duration Hydrocortisone — drug: 50mg of intravenous hydrocortisone will be administered every 6 hours for up to 7 days. · Shock-dependent hydrocortisone — drug: 50mg IV hydrocortisone every 6 hours while the patient is in septic shock · Fixed-duration higher dose Hydrocortisone — drug: 100mg of intravenous hydrocortisone will be administered every 6 hours for up to 7 days. · No antiviral agent for influenza — other: No antiviral agent intended to be active against influenza infection is to be administered · Five-days oseltamivir — drug: Oseltamivir administered enterally twice daily for 5 days or until hospital discharge (whichever occurs first) · Ten-days oseltamivir — drug: Oseltamivir administered enterally twice daily for 10 days or until hospital discharge (whichever occurs first) · No antiviral agent for COVID-19 — other: No antiviral agent intended to be active against SARS-CoV-2 infection is to be administered · Lopinavir / Ritonavir — drug: Lopinavir/ritonavir 400/100mg administered enterally, or 5ml 80/20mg per mL solution suspension via gastric tube, every 12 hours. · Hydroxychloroquine — drug: Loading dose of 800mg hydroxychloroquine administered enterally every 6 hours until 2 doses have been administered. · Hydroxychloroquine + lopinavir/ritonavir — drug: Lopinavir/ritonavir 400/100mg administered enterally, or 5ml 80/20mg per mL solution suspension via gastric tube, every 12 hours. · Ivermectin — drug: Ivermectin administered enterally at a dose of 0.2 mg/kg once daily with a maximum daily dose of 24mg/day. · No immune modulation for COVID-19 — other: No immune modulating agent intended to be active against COVID-19 is to be administered. · Interferon beta-1a — drug: IFN-β1a 10 μg will be administered as an intravenous bolus injection via a central or peripheral line. · Anakinra — drug: A loading dose of 300mg anakinra will be administered as a bolus via central or peripheral line. · Tocilizumab — drug: Tocilizumab will be administered as a single dose of 8mg/kg estimated or measured body weight, with a maximum total dose of 800mg. · Sarilumab — drug: Sarilumab will be administered as a single dose of 400mg, via IV infusion through peripheral or central line over a one-hour period. · Local standard venous thromboprophylaxis — drug: Standard venous thromboprophylaxis that complies with local guidelines or usual practice will be administered for 14 days following randomisation or until hospital discharge, whichever occurs first. · Therapeutic dose anticoagulation — drug: Patients will be administered either low molecular weight heparin (LMWH) or unfractionated heparin (UFH) to achieve systemic anticoagulation. · Conventional low dose thromboprophylaxis — drug: Low dose thromboprophylaxis will be administered for 14 days following randomisation or until hospital discharge, whichever occurs first. · Intermediate dose thromboprophylaxis — drug: Intermediate dose thromboprophylaxis will be administered for 14 days following randomisation or until hospital discharge, whichever occurs first. · Continuation of therapeutic dose anticoagulation — drug: Patients already receiving therapeutic dose anticoagulation at the time of randomisation to this intervention will be administered either unfractionated heparin by IV infusion or low-molecular weight heparin to achieve systemic anticoagulation according to local practice for acute VTE treatment for 14 days following randomisation or until hospital discharge, whichever occurs first. · No immunoglobulin — other: No immunoglobulin intended to be active against SARS-CoV-2 infection is to be administered. · Convalescent plasma — biological: Patients will receive at least one and no more than two units of ABO compatible convalescent plasma within 48 hours of randomisation. · Delayed administration of convalescent plasma — biological: Note: this intervention is now closed. · No vitamin C — other: No high dose intravenous vitamin C is to be administered Note: this intervention is now closed. · Vitamin C — drug: Intravenous Vitamin C 50mg/kg administered every 6 hours for 16 doses Note: this intervention is now closed. · No antiplatelet — other: No antiplatelet agent or NSAID to be administered. · Aspirin — drug: Aspirin administered at either 75mg or 100mg once per day for 14 days or until hospital discharge, whichever occurs first. · P2Y12 inhibitor — drug: Site-selected P2Y12 inhibitor: * Clopidogrel: administered 75 mg once per day for 14 days or until hospital discharge, whichever occurs first. · No simvastatin — other: No simvastatin intended to be active against COVID-19 is to be administered Note: this intervention is now closed. · Simvastatin — drug: Simvastatin 80mg administered once daily via enteral route, while the patient remains in hospital up to 28 days after randomisation Note: this intervention is now closed. · Eritoran — drug: Eritoran initiated with a 26.24 mg loading dose (6.56 mg/h IV for 4 hours), followed by a second 13.12 mg loading dose (6.56 mg/h IV for 2 hours) at 12 hours after initiation. · Apremilast — drug: Apremilast administered 30mg twice daily for 14 days or until hospital discharge, whichever occurs first. · Clinician-preferred mechanical ventilation strategy — procedure: Clinician-preferred ventilation strategy, including mode of ventilation and all ventilatory parameters · Protocolised mechanical ventilation strategy — procedure: Invasive mechanical ventilation strategy delivered as outlined in relevant protocol documents for this domain. · No renin-angiotensin system inhibitor — other: No RAS inhibitor (i.e. · Angiotensin converting enzyme inhibitor — drug: Site-preferred ACEi agent administered as directed by the treating clinician for 10 days or until hospital discharge, whichever occurs first. · Angiotensin Receptor Blockers — drug: Site-preferred ARB agent administered as directed by the treating clinician for 10 days or until hospital discharge, whichever occurs first. · ARB + DMX-200 — drug: Site-preferred ARB agent administered in combination with DMX-200 for 10 days or until hospital discharge, whichever occurs first. · No cysteamine — other: No cysteamine to be administered until the end of study day 10 or hospital discharge, whichever occurs first. · Cysteamine — drug: Cysteamine administered every 8 hours at a dose of 5 mg/kg estimated or measured body weight (maximum dose of 500mg), for ten days or until ICU discharge, whichever occurs first. · Fixed-duration dexamethasone — drug: 6 mg of IV or enteral dexamethasone will be administered daily for up to 10 days while in hospital. · Baloxavir Marboxil — drug: Baloxavir marboxil administered on days 1 and 4 post-randomisation. · Five-days oseltamivir + baloxavir marboxil — drug: Oseltamivir administered enterally twice daily for 5 days or until hospital discharge (whichever occurs first), in addition to baloxavir marboxil administered on days 1 and 4 post-randomisation. · Ten-days oseltamivir + baloxavir marboxil — drug: Oseltamivir administered enterally twice daily for 10 days or until hospital discharge (whichever occurs first), in addition to baloxavir marboxil administered on days 1 and 4 post-randomisation. · No endothelial modulator — other: No endothelial modulator (imatinib or another tyrosine kinase inhibitor targeting the same pathway as imatinib) is to be administered. · Imatinib — drug: Enteral imatinib will be administered as a single 800mg loading dose (study day 1) followed by 400mg daily until study day 14 or discharge. · No Immune Modulator for Influenza — other: No immune modulating agent intended to be active against influenza is to be administered. · Tocilizumab — drug: Tocilizumab will be administered as a single dose of 8mg/kg estimated or measured body weight, with a maximum total dose of 800mg. · Baricitinib — drug: Baricitinib will be administered at a dose that is determined by age and renal function, for up to 10 days or hospital discharge (whichever occurs first). · No antiviral agent for COVID-19 — other: No antiviral agent intended to be active against SARS-CoV-2 infection is to be administered · Nirmatrelvir/ritonavir — drug: Nirmatrelvir-ritonavir will be administered at a dose that is dependent on renal function, for five days. · Remdesivir — drug: Remdesivir is administered at 200 mg on day one followed by 100 mg daily for a further four doses (i.e., for five doses in total) or until hospital discharge, whichever occurs first. · Nirmatrelvir/ritonavir + remdesivir — drug: Nirmatrelvir-ritonavir will be administered at a dose that is dependent on renal function, for five days.

Patient visit burden

Not specified by the sponsor