High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy

• Status: Not yet recruiting
• Trial end date: 2021-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Randomized, controlled study conducted in hospitalized patients with severe COViD-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation.

Aim of this study is to assess whether high doses of Low Molecular Weight Heparin (LMWH) (ie. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (ie, Enoxaparin 4000 IU once day) are:

1. More effective to prevent clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first, during hospital stay:

1. Death

2. Acute Myocardial Infarction [AMI]

3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]

4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients who are in standard oxygen therapy by delivery interfaces at randomisation

5. Need for invasive mechanical ventilation for patients who are in non-invasive mechanical ventilation at randomisation

2. Similar in terms of major bleeding risk during hospital stay

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Azienda Ospedaliero-Universitaria di Modena
• Treatments: Enoxaparin

Criteria

Inclusion Criteria (all required):

• Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material)

• Severe pneumonia defined by the presence of at least one of the following criteria:

1. Respiratory Rate ≥25 breaths /min

2. Arterial oxygen saturation≤93% at rest on ambient air

3. PaO2/FiO2 ≤300 mmHg

• Coagulopathy, defined by the presence of at least one of the following criteria:

1. D-dimer >4 times the upper level of normal reference range

2. Sepsis-Induced Coagulopathy (SIC) score >4

• No need for invasive mechanical ventilation

Exclusion Criteria:

• Invasive mechanical ventilation

• Thrombocytopenia (platelet count < 80.000 mm3)

• Coagulopathy: INR >1.5, aPTT ratio > 1.4

• Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min)

• Known hypersensitivity to enoxaparin

• History of heparin induced thrombocytopenia

• 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)

• Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves).

• Concomitant double antiplatelet therapy

• Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed

• Pregnancy or breastfeeding or positive pregnancy test

• Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition)

• Lack or withdrawal of informed consent