Clinical trial NCT05036824: Intensive Dose Tinzaparin in Hospitalized COVID-19 Patients
Official title: Intensive Dose Tinzaparin in Hospitalized COVID19 Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Covid19
Hospitalization
Keywords: SARS-CoV-2
Tinzaparin
LMWH
COVID-19
Lead sponsor: University Hospital of Patras
Sponsor class: OTHER
First posted: 2021-09-08
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Hospitalized patients with COVID-19 infection administered thromboprophylaxis with tinzaparin

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.

Eligibility criteria: Inclusion Criteria

1. Patients admitted to hospital with COVID-19, PCR+ SARS-CoV-2 infection (from any specimen) administered thromboprophylaxis with tinzaparin in intermediate or therapeutic dose
2. Age ≥ 18 years
3. Signed informed consent

Exclusion Criteria

1. Patients admitted to ICU with COVID-19, PCR+ SARS-CoV-2 infection (from any specimen)
2. Age \< 18 years
3. Pregnancy
4. Current diagnosis or suspicion of pulmonary thromboembolism or deep vein thrombosis
5. Progression to death was imminent and inevitable within 24 hours from the admission, irrespective of the provision of treatments
6. Not signed informed consent

Primary outcomes:
measure: Incidence of thrombotic events
timeFrame: through study completion, an average of 6 months
measure: Incidence of bleeding events
timeFrame: through study completion, an average of 6 months
Secondary outcomes:
measure: WHO progression scale
timeFrame: through study completion, an average of 6 months
measure: Length of hospital stay
timeFrame: through study completion, an average of 6 months
Other outcomes:
Locations:
city: Patras
country: Greece
facility: University Hospital of Patras
state: Achaia
city: Athens
country: Greece
facility: Evangelismos General Hospital
state: Attica
city: Athens
country: Greece
facility: General Hopital Elpis
state: Attica
city: Ioannina
country: Greece
facility: University General Hospital of Ioannina
state: Epirus
city: Korfu
country: Greece
facility: General Hospital of Kerkira "Ag. Irini"
state: Ionian Islands
city: Kozáni
country: Greece
facility: General Hospital of Kozani "Mamatsio"
state: Macedonia
city: Patras
country: Greece
facility: Genereal Hospital of Patras "Ag. Andreas"
state: Peloponnese
Study officials:
affiliation: University Hospital of Patras
name: Karolina Akinosoglou, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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