Intensive Dose Tinzaparin in Hospitalized COVID-19 Patients

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to evaluate the current management approach with intermediate or therapeutic doses of tinzaparin for thromboprophylaxis in hospitalized patients, non on ICU organ support, with confirmed COVID-19.

Detailed Description
-----------------
A prothrombotic state, attributable to a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and leading to activation of the coagulation cascade, is a recognized feature of Coronavirus disease 2019 (COVID-19) infection. This can manifest in venous thromboembolism (VTE), arterial thrombosis events (ATE), and disseminated intravenous coagulation (DIC) and coagulopathy are reflective of more severe disease and adverse prognosis. A significant number of patients with COVID-19 require single or multiple organ support on the Intensive Care Unit (ICU), estimated to be between 12 and 17% of patients. with the reported mortality in these cohorts between 25 and 40%. International guidelines recommend that hospitalized patients with COVID-19 should receive pharmacological prophylaxis against VTE, in the absence of contraindications. With respect to how VTE prophylaxis is achieved, Low Molecular Weight Heparins (LMWH), in addition to their well-known anticoagulant properties, appear to have additional antiviral and anti-inflammatory effects that may be potentially beneficial in hospitalized COVID-19 patients. Though international and national guidelines state that all hospitalized patients with COVID-19 should receive pharmacologic thromboprophylaxis, the rising incidence of thrombotic complications in COVID-19 patients has led a lot of hospitals to adopt the strategy of increasing the dose of anticoagulation for prophylaxis to 'intermediate' or therapeutic doses using a risk-adapted strategy with increased doses administration based on factors associated with increased risk; clinicians weigh the benefits and risks of therapeutic anticoagulation in terms of thrombosis and major bleeding risk for individual patients. Additionally, LMWHs have different physicochemical characteristics as a result of the diverse methods of their manufacturing. The variations in molecular composition and pharmacological properties of LMWHs are reflected in differences in their clinical efficacy and safety. Each LMWH should, therefore, be considered as a unique substance. Tinzaparin is the only LMWH known that is prepared by enzymatic hydrolysis with heparinase. Due to its preparation method, tinzaparin has distinct properties than other LMWHs including and not limited to: higher Anti-IIa activity and Anti-Xa/Anti-IIa activity ratio, the higher release of Tissue Factor Pathway Inhibitor (TFPI), less dependence from renal function for its clearance, and more complete neutralization from its antidote, if needed. Due to the key role of increased Thrombin generation (IIa) and Tissue factor (TF) pathway activation in COVID-19-associated thrombosis , special properties of tinzaparin in Anti-IIa activity and TFPI production and release from endothelial cells, as well as significant effects of TFPI in various vascular, inflammatory, cardiovascular, hematological and oncological disorders, tinzaparin could have an expanded role beyond its well-known anticoagulant function. The purpose of this study is to evaluate the overall clinical effectiveness and safety of 'intermediate' or therapeutic doses of anticoagulation with tinzaparin administered for thromboprophylaxis in COVID-19 patients with moderate disease severity during hospitalization in Greek hospitals.

Official Title
-----------------
Intensive Dose Tinzaparin in Hospitalized COVID19 Patients

Conditions
-----------------
Covid19, Hospitalization

Intervention / Treatment
-----------------
* Drug: tinzaparin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Patients admitted to hospital with COVID-19, PCR+ SARS-CoV-2 infection (from any specimen) administered thromboprophylaxis with tinzaparin in intermediate or therapeutic dose Age ≥ 18 years Signed informed consent Exclusion Criteria Patients admitted to ICU with COVID-19, PCR+ SARS-CoV-2 infection (from any specimen) Age < 18 years Pregnancy Current diagnosis or suspicion of pulmonary thromboembolism or deep vein thrombosis Progression to death was imminent and inevitable within 24 hours from the admission, irrespective of the provision of treatments Not signed informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19 patients<br>Patients admitted to hospital with COVID-19, PCR+ SARS-CoV-2 infection administered thromboprophylaxis with tinzaparin. Dosage: intermediate or therapeutic dose Frequency of tinzaparin administration: once daily Duration: Unknown | Drug: tinzaparin<br>* Daily tinzaparin administration: 8000 - 14000 Anti-Xa IU<br>* Other names: Innohep;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of thrombotic events | Evaluate the incidence of thrombotic events: total & per type e.g. PE, DVT, symptomatic, incidental, proximal, distant etc. (Measured as percentage of events in relation to the study population) | through study completion, an average of 6 months | 
| Incidence of bleeding events | Evaluate τηε ιncidence of bleeding events (total & per type e.g. Major, CRNMB and minor) (Measured as percentage of events in relation to the study population) | through study completion, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WHO progression scale | Evaluate the patients in relation to World Health Organization (WHO) progression scale (range from 0 (healthy) to 10 (death); values below or equal to 5 correspond to the absence of any oxygen supply beside nasal or facial mask). | through study completion, an average of 6 months | 
| Length of hospital stay | Evaluate the length of hospital stay (in days) | through study completion, an average of 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SARS-CoV-2, Tinzaparin, LMWH, COVID-19