Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol

To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized patients with COVID19 not requiring Invasive Mechanical Ventilation [IMV], are: a)more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: 1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were receiving standard oxygen therapy5.IMV in patients who at randomisation were receiving non-invasive mechanical ventilationb)Similar in terms of major bleeding risk TRIAL DESIGN: Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study. Inpatients will be recruited from 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit. 1. Age > 18 and < 80 years 2. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 3. Severe pneumonia defined by the presence of at least one of the following criteria: a.Respiratory Rate ≥25 breaths /minb.Arterial oxygen saturation≤93% at rest on ambient airc.PaO2/FiO2 ≤300 mmHg 4. Coagulopathy, defined by the presence of at least one of the following criteria: a.D-dimer >4 times the upper level of normal reference rangeb.Sepsis-Induced Coagulopathy (SIC) score >4 5. No need of IMV EXCLUSION CRITERIA: 1. Age 80 years 2. IMV 3. Thrombocytopenia (platelet count < 80.000 mm3) 4. Coagulopathy: INR >1.5, aPTT ratio > 1.4 5. Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min) 6. Known hypersensitivity to enoxaparin 7. History of heparin induced thrombocytopenia 8. Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations) 9. Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves) 10. Concomitant double antiplatelet therapy 11. Administration of therapeutic doses of LMWH, fondaparinux, o