Enoxaparin at Prophylactic or Therapeutic Doses in COVID-19 (EMOS-COVID)

ASST Fatebenefratelli Sacco

Status and phase: Completed; Phase 3

Conditions: Thrombosis; Covid19

Treatments: Drug: Enoxaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT04646655

HLS-02COVID19/2020

Details and patient eligibility

About

SINGLE CENTER PHASE III INTERVENTIONAL RANDOMIZED CONTROLLED TRIAL comparing efficacy and safety of enoxaparin at prophylactic dose (standard treatment) and enoxaparin at therapeutic dose (OFF-LABEL treatment) in 300 COVID-19 infected patients with moderate-severe respiratory failure (PaO2/FiO2<250) and/or increased D-dimer levels enrolled in different Units (Infectious disease, Internal Medicine, Emergency Medicine, Pneumology) of Azienda Socio Sanitaria Territoriale Fatebenefratelli Sacco (ASST-FBF-SACCO).

Full description

Patients with COVID-19 are at high risk of developing a venous thromboembolism (VTE) and it is essential that effective thromboprophylaxis with parenteral drugs (LMWH, UFH) is considered for all patients admitted to hospital especially in case of severe pneumonia.

The aim of the study is the evaluation of efficacy and safety of enoxaparin at prophylactic dose (standard treatment) as compared to enoxaparin at therapeutic dose (OFF-LABEL treatment) in 300 COVID-19 infected patients with moderate-severe respiratory failure (PaO2/FiO2<250) and/or increased D-dimer levels.

After the admission to different Units (Infectious disease, Internal Medicine, Emergency Medicine, Pneumology), enoxaparin at prophylactic dose (standard of care) will be prescribed to all patients.

The randomization of the single patient will be made when the the inclusion criteria (PaO2/FiO2 <250 and/or D-dimer >2000 ng/) will be satisfied. Patients with increased bleeding risk will be excluded (exclusion criteria).

Patients will be divided into two arms:

• arm A: enoxaparin at prophylactic dose (standard 4.000 IU; 6000 UI if body weight>100 kg)
• arm B: enoxaparin at therapeutic dose (70 U/Kg b.i.d. every 12 h)

In both arms, enoxaparin treatment will be monitored clinically and with first and second line laboratory tests Venous compression ultrasound (CUS) will be performed at admission and after 7 days in case of a first negative exam and elevated D-Dimer levels, to rule out deep vein thrombosis.

Enoxaparin at prophylactic dose (4000 IU) will be maintained in all patients for 4 weeks after discharge.

Enrollment: 142 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• COVID-19 related pneumonia with moderate-severe respiratory failure (PaO2/FiO2<250) and/or markedly increased D-dimer level (>2000 ng/mL)
• Signed informed consent

Exclusion criteria

• age < 18 and > 80 yrs
• history of bleeding (peptic ulcer, esophageal varices, cerebral aneurysm, cancer at high risk of bleeding, cirrhosis, hemorrhagic stroke < 1 year)
• thrombocytopenia (<100 x109/L)
• anemia (Hb < 8 g/dl)
• coagulation abnormalities (PT e/o aPTT > 1.5; fibrinogen < 150 mg/dl)
• consumption coagulopathy (ISTH criteria) [15, 16]
• deep vein thrombosis or pulmonary embolism
• dual antiplatelet therapy
• ongoing anticoagulant therapy
• allergic reaction to LMWH
• previous heparin-induced thrombocytopenia
• major surgery < 1 month; neurosurgery <3 months; eye surgery <3 months
• pregnancy
• arterial hypertension (SBPS>160 mm Hg; DBP>100 mm Hg)
• renal failure (creatinine clearance 30 ml/min)
• ICU admission or endotracheal intubation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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142 participants in 2 patient groups

Enoxaparin at prophylactic dose

Active Comparator group

Description:

Enoxaparin at prophylactic dose: standard 4.000 IU QD via subcutaneous injection (6000 IU if body weight\>100 kg)

Treatment:

Drug: Enoxaparin

Enoxaparin at therapeutic dose

Experimental group

Description:

Enoxaparin at therapeutic dose : 70 U/Kg b.i.d. (every 12 h) In order to easily calculate the correct therapeutic dose of enoxaparin for each patient, a simplified categorization will be applied, as follows: * weight \< 65 Kg: 4.000 IU b.i.d. (every 12 h) * weight ≥ 65 Kg: 6.000 IU b.i.d. (every 12 h) * weight ≥ 100 Kg: 8.000 IU b.i.d. (every 12 h) The most appropriate dose will be evaluated in patients with creatinine clearance between 30 and 50 ml/min

Treatment:

Drug: Enoxaparin