This is an international, open-label, stratified randomized controlled trial with Bayesian adaptive stopping rules to compare the effects of therapeutic-dose heparin vs. usual care pharmacological thromboprophylaxis on outcomes in patients admitted to hospital with community acquired pneumonia (CAP).
Patients ≥18 years of age
Radiographic evidence of new or worsening infiltrate
One or more of the following signs and/or symptoms of lower respiratory tract infection
Requires supplemental oxygen to treat hypoxemia (or requires an increased level of supplemental oxygen if on chronic oxygen therapy)
Suspected or confirmed active COVID-19 infection
Hospital admission for >72 hours prior to randomization
Patients receiving non-invasive or invasive ventilation, vasopressors, or extracorporeal life support (ECLS) within an ICU at the time of enrollment
Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization
Parallel
Heparin
DrugPreference is for LMWH given ease of administration and possibility of a more favorable safety profile, if no contraindication is present. Enoxaparin, dalteparin, or tinzaparin are acceptable LMWHs to be used for patients in the investigational arm and dose should be based on measured or estimated weight of the patient. Alternatively, intravenous UFH may be used and may be preferred in the presence of significant renal compromise. Intravenous UFH is typically dosed according to total body weight and pragmatically adjusted according to local institutional policy to achieve an activated partial thromboplastin time (aPTT) of 1.5-2.5x the reference value, or a corresponding UFH anti-Xa level. If UFH is used, the availability of a local site policy that specifies an aPTT target in this range or a corresponding anti-Xa value is a requirement.
Ordinal endpoint reflecting survival
Survival to hospital discharge without ICU-level organ support. Organ support is defined as receipt of high flow nasal oxygen, invasive or non-invasive mechanical ventilation, vasopressor/inotropic therapy, or extracorporeal life support (ECLS) within an ICU. This outcome reflects disease progression to ICU-level organ failure or the worst possible outcome (death). It was chosen because of its importance to patients, clinicians, and other stakeholders. Given the limited number of ICU beds, reducing the burden of critical illness has important health system capacity implications.
Bleeding events
Number of participants with major bleeds as defined by the ISTH definition.
HIT events
Number of participants with laboratory confirmed heparin induced thrombocytopenia (HIT)
Thrombotic events
Number of participants with deep vein thrombosis, pulmonary embolism, systemic arterial thromboembolism, myocardial infarction, or ischemic stroke
Invasive mechanical ventilation
Ordered categorical endpoint with three possible outcomes based on the worst status of each patient through day 30 following randomization
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University of Manitoba
Lead sponsor
Canadian Institutes of Health Research (CIHR)
Collaborator
Research Manitoba
Collaborator
Ozmosis Research Inc.
Collaborator
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
Collaborator
Canadian Critical Care Trials Group
Collaborator
AVANTI
Collaborator
Aurora Clinical Research
Collaborator
