Enoxaparin at Prophylactic or Therapeutic Doses in COVID-19

ASST Fatebenefratelli Sacco142 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

142

Conditions

Covid19 Thrombosis

Interventions

EnoxaparinDRUG

subcutaneous injections

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (1)

ASST Fatebenefratelli Sacco

Milan, Italy

Outcomes

Primary Outcomes

Mortality rate

Mortality registered during the time frame

Time frame: 30 days from enrollment

Progression of respiratory failure

Progression of respiratory failure defined as duration of continuous positive pressure ventilation (CPAP)

Time frame: 30 days from enrollment

Progression of respiratory failure

Progression of respiratory failure defined as percentage of patients admitted to ICU

Time frame: 30 days from enrollment

Progression of respiratory failure

Progression of respiratory failure defined as percentage of patients undergoing oro-tracheal intubation

Time frame: 30 days from enrollment

Number of major bleeding episodes

Major bleeding (ISTH criteria) and/or clinically relevant non-major bleeding

Time frame: up to 6 months from randomization

Secondary Outcomes

Respiratory function improvement

Amelioration of the respiratory function defined as a PaO2/FiO2 increase \> 300 and / or respiratory rate (RR) \< 20 breaths per min

Time frame: at 72 hours

Respiratory function improvement

Amelioration of the respiratory function defined as a PaO2/FiO2 increase \> 300 and / or respiratory rate (RR) \< 20 breaths per min

Time frame: 1 week from randomization

Number of major cardiovascular events

Data from ClinicalTrials.gov

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