INTERACT: Intensive Dose Tinzaparin in Hospitalized COVID-19 Patients

Sponsor

University Hospital of Patras (Other)

Overall Status

Recruiting

CT.gov ID

NCT05036824

Collaborator

(none)

300

Enrollment

Locations

6.9

Anticipated Duration (Months)

42.9

Patients Per Site

6.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Hospitalization	Drug: tinzaparin

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Case-Only

Time Perspective:

Retrospective

Official Title:

Intensive Dose Tinzaparin in Hospitalized COVID19 Patients

Anticipated Study Start Date :

Oct 1, 2021

Anticipated Primary Completion Date :

Mar 31, 2022

Anticipated Study Completion Date :

Apr 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
COVID-19 patients 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 Daily tinzaparin administration: 8000 - 14000 Anti-Xa IU Other Names: Innohep

Arm

Intervention/Treatment

COVID-19 patients

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

Daily tinzaparin administration: 8000 - 14000 Anti-Xa IU

Other Names:

Innohep

Outcome Measures

Primary Outcome Measures

Incidence of thrombotic events [through study completion, an average of 6 months]
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)
Incidence of bleeding events [through study completion, an average of 6 months]
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)

Secondary Outcome Measures

WHO progression scale [through study completion, an average of 6 months]
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).
Length of hospital stay [through study completion, an average of 6 months]
Evaluate the length of hospital stay (in days)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Patras	Patras	Achaia	Greece	26504
2	Evangelismos General Hospital	Athens	Attica	Greece	10676
3	General Hopital Elpis	Athens	Attica	Greece	11522
4	University General Hospital of Ioannina	Ioannina	Epirus	Greece	45500
5	General Hospital of Kerkira "Ag. Irini"	Korfu	Ionian Islands	Greece	49100
6	General Hospital of Kozani "Mamatsio"	Kozáni	Macedonia	Greece	50100
7	Genereal Hospital of Patras "Ag. Andreas"	Patras	Peloponnese	Greece	26335