D-dimer Adjusted Versus Therapeutic Dose Low-molecular-weight Heparin in Patients With COVID-19 Pneumonia

Study Overview
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Brief Summary
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evaluation of the efficacy and safety of D-dimer adjusted heparin versus therapeutic dose heparin in patients with COVID-19 Pneumonia.

Detailed Description
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The following will be done for enrolled patients: Data collection: name, age, sex, special habits of medical importance (i.e. smoking, drug abuse), comorbid conditions. Clinical examination Vital data Local chest examination Measurement of oxygen saturation using pulse oximeter Laboratory investigations: Complete blood count with differential count Liver and kidney functions D-dimer level Coagulation profile Radiology work up ( Chest X-ray-High resolution computed tomography of the chest- computed tomography of the chest with pulmonary angiography as needed) Sepsis-induced coagulopathy score (SIC score) Sequential organ failure score (SOFA score) Patients will receive treatment according to the hospital guidelines for different disease stratification severity

Official Title
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D-dimer Adjusted Versus Therapeutic Dose Low-molecular-weight Heparin in Patients With COVID-19 Pneumonia

Conditions
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Coronavirus Disease (COVID)19

Intervention / Treatment
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* Drug: low-molecular-weight heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult (>18 years) patients from both sexes with COVID-19 pneumonia with positive nucleic acid test for severe acute respiratory syndrome Coronavirus (SARS-CoV-2) hospitalized either in the ward or intensive care unit Exclusion Criteria: Patients with absolute contraindication of pharmacological thromboprophylaxis and/ anticoagulation Congenital hemorrhagic disorders Hypersensitivity to heparin Personal history of heparin-induced thrombocytopenia Active major bleeding or conditions predisposing to major bleeding. Major bleeding is defined as fulfilling any one of these three criteria: a) occurs in a critical area or organ (e.g.intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, intra-uterine or intramuscular with compartment syndrome), b) causes a fall in haemoglobin level (Hb) of ≥2g/dL in a 24h period, or c) leads to transfusion of 2 or more units of whole blood or red blood cells (13). Suspected or confirmed bacterial endocarditis Ongoing or planned therapeutic anticoagulation for any other indication Platelet count <50,000/μL within the past 24 hours or Hb level <8g/dL Prothrombin time (PT) ≥2 seconds above the upper limit of age-appropriate local reference range within the past 24 hours Activated partial thromboplastin time (aPTT) ≥4 seconds above the upper limit of age-appropriate local reference range within the past 24 hours Fibrinogen <2.0 g/L Severe renal impairment (CrCl<30 mL/min) or acute kidney injury Use of dual antiplatelet therapy Pregnancy Unwillingness to consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Therapeutic dose low-molecular-weight heparin (LMWH)<br>Therapeutic dose low-molecular-weight heparin from admission until the end of hospital stay Enoxaparin 1 mg/kg subcutaneous every 12 hours | Drug: low-molecular-weight heparin<br>* low-molecular-weight heparin administered via subcutaneous injection<br>* Other names: Enoxaparin;|
| Experimental: D-dimer levels and weight adjusted low-molecular-weight heparin (LMWH)therapy<br>from admission until the end of hospital stay. Patients will be stratified according to their body weight and D-dimer level and receive LMWH D-Dimer level Body Weight LMWH dose <1 mg/dl <100kg Enoxaparin 40mg OD 100-150kg Enoxaparin 40mg BD >150kg Enoxaparin 60mg BD 1-3 mg/ dl <100kg Enoxaparin 40mg BD 100-150kg Enoxaparin 80mg BD >150kg Enoxaparin 120mg BD >3 mg/ dl Enoxaparin 80mg BD | Drug: low-molecular-weight heparin<br>* low-molecular-weight heparin administered via subcutaneous injection<br>* Other names: Enoxaparin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | All cause mortality | Until patient is discharged or up to 4 weeks whichever comes first | 
| occurrence of venous and/or arterial thrombosis | clinical signs supported by radiological evidence of arterial thrombosis or venous thromboembolism (e.g. venous or arterial duplex and CT scan of the chest with pulmonary angiography) | Until patient is discharged or up to 4 weeks whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence of Sepsis-induced coagulopathy | calculation of sepsis induced coagulopathy (SIC) score | Until patient is discharged or up to 4 weeks whichever comes first | 
| Occurrence of adult respiratory distress syndrome (ARDS) | Calculation of partial pressure of arterial oxygen/ fraction of inspired oxygen (PaO2/ FIO2) ratio | Until patient is discharged or up to 4 weeks whichever comes first | 
| Occurrence of sepsis | Calculation of sequential organ failure (SOFA) score | Until patient is discharged or up to 4 weeks whichever comes first | 
| ICU admission and need for mechanical ventilation | occurrence of respiratory failure detected by arterial blood gases analysis | Until patient is discharged or up to 4 weeks whichever comes first |