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).

The global incidence of hospitalization due to CAP is high and associated with substantive morbidity and mortality. Thrombotic complications - including venous, arterial, and possibly microvascular - occur commonly in hospitalized patients across many etiologies of CAP. Poor outcomes may be mediated by both inflammatory and thrombotic processes leading to respiratory, cardiac, and other end organ dysfunction. There are currently no established therapies that modify the potentially maladaptive immunothrombosis pathway in CAP.

Therapeutic-dose anticoagulation with heparin reduces disease progression and mortality in non-critically ill patients hospitalized with COVID-19 with an acceptable safety profile. COVID-19 shares pathogenic features, including activation of the inflammatory and coagulation cascades, with other pneumonias. Whether therapeutic-dose heparin confers similar clinical benefits in non-COVID-19 CAP is unknown.

Inclusion Criteria:

1. Patients ≥18 years of age

2. Admitted to hospital for a suspected or confirmed diagnosis of CAP defined by:

   1. Radiographic evidence of new or worsening infiltrate
   2. One or more of the following signs and/or symptoms of lower respiratory tract infection

   i. New or increased cough or sputum production ii. Fever of > 37.8C or temperature < 36C iii. WBC > 11 x 109/L or < 4 x 109/L c. The primary diagnosis is believed to be CAP as per the attending physician

3. Requires supplemental oxygen to treat hypoxemia (or requires an increased level of supplemental oxygen if on chronic oxygen therapy)

4. Hospital admission anticipated to last ≥72 hours from randomization

Exclusion Criteria:

1. Suspected or confirmed active COVID-19 infection

2. Hospital admission for >72 hours prior to randomization

3. Patients receiving non-invasive or invasive ventilation, vasopressors, or extracorporeal life support (ECLS) within an ICU at the time of enrollment

4. Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization

5. Patients for whom the intent is to not use pharmacologic thromboprophylaxis

6. Patients with an independent indication for therapeutic-dose anticoagulation

7. Patients with a contraindication to therapeutic-dose anticoagulation, including:

   1. Non-traumatic bleeding that requires medical evaluation or hospitalization within 30 days prior to CAP hospital admission
   2. History of an inherited or acquired bleeding disorder
   3. Cerebral aneurysm or mass lesions of the central nervous system
   4. Ischemic stroke within 3 months of hospital admission
   5. Gastrointestinal bleeding within 3 months of hospital admission
   6. Platelet count <50 x109/L OR INR >2.0 OR hemoglobin <80 g/L at the time of screening
   7. Other physician-perceived contraindications to therapeutic anticoagulation

8. History of heparin induced thrombocytopenia (HIT) or other heparin allergy

9. Current or recent (within 7 days of screening) use of dual anti-platelet inhibitors (For example; Aspirin + one of the following; clopidogrel, ticagrelor, prasugrel)

10. Patients in whom imminent death is anticipated

11. Anticipated transfer to another hospital that is not a study site within 72 hours of randomization

12. Enrollment in other interventional trials related to anticoagulation or antiplatelet therapy during current hospitalization