Intensive Dose Tinzaparin in Hospitalized COVID-19 Patients

Covid19 Clinical Trial

— INTERACT  

Official title:

Intensive Dose Tinzaparin in Hospitalized COVID19 Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05036824
• Other study ID #: 18634/23-7-2021 pend. aprooval
• Status: Recruiting
• Start date: October 1, 2021
• Est. completion date: April 30, 2022

Study information

• Verified date: September 2021
• Source: University Hospital of Patras
• Contact: Karolina Akinosoglou, MD,PhD
• Phone: +306977762897
• Email: akin[@]upatras.gr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: April 30, 2022
• Est. primary completion date: March 31, 2022
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Covid19
• Hospitalization

Intervention

Drug:
• tinzaparin
Daily tinzaparin administration: 8000 - 14000 Anti-Xa IU

Locations

Country	Name	City	State
Greece	Evangelismos General Hospital	Athens	Attica
Greece	General Hopital Elpis	Athens	Attica
Greece	University General Hospital of Ioannina	Ioannina	Epirus
Greece	General Hospital of Kerkira "Ag. Irini"	Korfu	Ionian Islands
Greece	General Hospital of Kozani "Mamatsio"	Kozáni	Macedonia
Greece	Genereal Hospital of Patras "Ag. Andreas"	Patras	Peloponnese
Greece	University Hospital of Patras	Patras	Achaia

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital of Patras

Country where clinical trial is conducted

Greece, 

References & Publications (18)

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Moores LK, Tritschler T, Brosnahan S, Carrier M, Collen JF, Doerschug K, Holley AB, Jimenez D, Le Gal G, Rali P, Wells P. Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report. Chest. 2020 Sep;158(3):1143-1163. doi: 10.1016/j.chest.2020.05.559. Epub 2020 Jun 2. — View Citation

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Poterucha TJ, Libby P, Goldhaber SZ. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017 Feb 28;117(3):437-444. doi: 10.1160/TH16-08-0620. Epub 2016 Dec 15. Review. — View Citation

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Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium, Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775. Erratum in: JAMA. 2020 May 26;323(20):2098. — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Incidence of bleeding events	Evaluate t?e ?ncidence 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	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
Secondary	Length of hospital stay	Evaluate the length of hospital stay (in days)	through study completion, an average of 6 months