Covid19, Thrombosis
Conditions
Keywords
COVID.19, Thrombosis, Enoxaparin, Outcome, Respiratory failure, D-dimer, Venous compression ultrasound
Brief summary
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).
Detailed 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.
Interventions
DRUGEnoxaparin
subcutaneous injections
Sponsors
Massimo Arquati
Riccardo Colombo
Umberto Russo
Manuela Nebuloni
Spinello Antinori
ASST Fatebenefratelli Sacco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality rate | 30 days from enrollment | Mortality registered during the time frame |
| Progression of respiratory failure | 30 days from enrollment | Progression of respiratory failure defined as duration of continuous positive pressure ventilation (CPAP) |
| Number of major bleeding episodes | up to 6 months from randomization | Major bleeding (ISTH criteria) and/or clinically relevant non-major bleeding |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory function improvement | at 72 hours | Amelioration of the respiratory function defined as a PaO2/FiO2 increase \> 300 and / or respiratory rate (RR) \< 20 breaths per min |
| Number of major cardiovascular events | 6 months from randomization | numbers of myocardial infarction and stroke within the time frame |
| Deep Vein Thrombosis | 6 months from randomization | Numbers of Deep Vein Thrombosis at CUS examination within the time frame |
Countries
Italy
Outcome results
None listed