Intensive Dose Tinzaparin in Hospitalized COVID-19 Patients (INTERACT)
Intensive Dose Tinzaparin in Hospitalized COVID19 Patients
Přehled studie
Detailní popis
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.
Typ studie
Zápis (Očekávaný)
Kontakty a umístění
Studijní kontakt
- Jméno: Karolina Akinosoglou, MD,PhD
- Telefonní číslo: +306977762897
- E-mail: akin@upatras.gr
Studijní místa
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Achaia
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Patras, Achaia, Řecko, 26504
- Nábor
- University Hospital of Patras
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Kontakt:
- Karolina Akinosoglou, Ass. Prof.
- Telefonní číslo: +30 2610997254
- E-mail: akin@upatras.gr
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Attica
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Athens, Attica, Řecko, 10676
- Nábor
- Evangelismos General Hospital
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Kontakt:
- George Marakomichelakis, M.D. Ph.D.
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Dílčí vyšetřovatel:
- Christine Vadala, M.D. Ph.D.
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Athens, Attica, Řecko, 11522
- Nábor
- General Hopital Elpis
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Kontakt:
- Spyridon Savvanis, M.D. Ph.D
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Epirus
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Ioannina, Epirus, Řecko, 45500
- Nábor
- University General Hospital of Ioannina
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Kontakt:
- Haralampos ] Milionis, Ass. Prof.
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Ionian Islands
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Korfu, Ionian Islands, Řecko, 49100
- Nábor
- General Hospital of Kerkira "Ag. Irini"
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Kontakt:
- Ilias Papanicolaou, M.D. Ph.D.
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Macedonia
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Kozáni, Macedonia, Řecko, 50100
- Nábor
- General Hospital of Kozani "Mamatsio"
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Kontakt:
- Efthalia Randou, M.D. Ph.D.
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Peloponnese
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Patras, Peloponnese, Řecko, 26335
- Nábor
- Genereal Hospital of Patras "Ag. Andreas"
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Kontakt:
- George Efremidis, M.D. Ph.D.
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-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Metoda odběru vzorků
Studijní populace
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
Kohorty a intervence
Skupina / kohorta |
Intervence / Léčba |
|---|---|
|
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 |
Daily tinzaparin administration: 8000 - 14000 Anti-Xa IU
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Incidence of thrombotic events
Časové okno: 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)
|
through study completion, an average of 6 months
|
|
Incidence of bleeding events
Časové okno: 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)
|
through study completion, an average of 6 months
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
WHO progression scale
Časové okno: 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).
|
through study completion, an average of 6 months
|
|
Length of hospital stay
Časové okno: through study completion, an average of 6 months
|
Evaluate the length of hospital stay (in days)
|
through study completion, an average of 6 months
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Karolina Akinosoglou, MD,PhD, University Hospital of Patras
Publikace a užitečné odkazy
Obecné publikace
- Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, Nigoghossian C, Ageno W, Madjid M, Guo Y, Tang LV, Hu Y, Giri J, Cushman M, Quere I, Dimakakos EP, Gibson CM, Lippi G, Favaloro EJ, Fareed J, Caprini JA, Tafur AJ, Burton JR, Francese DP, Wang EY, Falanga A, McLintock C, Hunt BJ, Spyropoulos AC, Barnes GD, Eikelboom JW, Weinberg I, Schulman S, Carrier M, Piazza G, Beckman JA, Steg PG, Stone GW, Rosenkranz S, Goldhaber SZ, Parikh SA, Monreal M, Krumholz HM, Konstantinides SV, Weitz JI, Lip GYH; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Jun 16;75(23):2950-2973. doi: 10.1016/j.jacc.2020.04.031. Epub 2020 Apr 17.
- Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? Lancet. 2020 Apr 11;395(10231):1225-1228. doi: 10.1016/S0140-6736(20)30627-9. Epub 2020 Mar 13.
- Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA. 2020 Apr 28;323(16):1545-1546. doi: 10.1001/jama.2020.4031. No abstract available.
- 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.
- Thachil J. The versatile heparin in COVID-19. J Thromb Haemost. 2020 May;18(5):1020-1022. doi: 10.1111/jth.14821. Epub 2020 Apr 27. No abstract available.
- 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.
- Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, Holden KA, Read JM, Dondelinger F, Carson G, Merson L, Lee J, Plotkin D, Sigfrid L, Halpin S, Jackson C, Gamble C, Horby PW, Nguyen-Van-Tam JS, Ho A, Russell CD, Dunning J, Openshaw PJ, Baillie JK, Semple MG; ISARIC4C investigators. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020 May 22;369:m1985. doi: 10.1136/bmj.m1985.
- Arachchillage DRJ, Laffan M. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 May;18(5):1233-1234. doi: 10.1111/jth.14820. No abstract available.
- 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.
- Spyropoulos AC, Levy JH, Ageno W, Connors JM, Hunt BJ, Iba T, Levi M, Samama CM, Thachil J, Giannis D, Douketis JD; Subcommittee on Perioperative, Critical Care Thrombosis, Haemostasis of the Scientific, Standardization Committee of the International Society on Thrombosis and Haemostasis. Scientific and Standardization Committee communication: Clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020 Aug;18(8):1859-1865. doi: 10.1111/jth.14929. No abstract available.
- Fegan CD. Tinzaparin as an antithrombotic: an overview. Hosp Med. 1998 Feb;59(2):145-8.
- Linhardt RJ, Gunay NS. Production and chemical processing of low molecular weight heparins. Semin Thromb Hemost. 1999;25 Suppl 3:5-16.
- Matzsch T, Bergqvist D, Hedner U, Ostergaard P. Effects of an enzymatically depolymerized heparin as compared with conventional heparin in healthy volunteers. Thromb Haemost. 1987 Feb 3;57(1):97-101.
- Padilla A, Gray E, Pepper DS, Barrowcliffe TW. Inhibition of thrombin generation by heparin and low molecular weight (LMW) heparins in the absence and presence of platelet factor 4 (PF4). Br J Haematol. 1992 Oct;82(2):406-13. doi: 10.1111/j.1365-2141.1992.tb06437.x.
- McFadyen JD, Stevens H, Peter K. The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications. Circ Res. 2020 Jul 31;127(4):571-587. doi: 10.1161/CIRCRESAHA.120.317447. Epub 2020 Jun 26.
- Bajaj MS, Bajaj SP. Tissue factor pathway inhibitor: potential therapeutic applications. Thromb Haemost. 1997 Jul;78(1):471-7.
- Kaiser B, Hoppensteadt DA, Fareed J. Tissue factor pathway inhibitor: an update of potential implications in the treatment of cardiovascular disorders. Expert Opin Investig Drugs. 2001 Nov;10(11):1925-35. doi: 10.1517/13543784.10.11.1925.
- Bochenek J, Puskulluoglu M, Krzemieniecki K. The antineoplastic effect of low-molecular-weight heparins - a literature review. Contemp Oncol (Pozn). 2013;17(1):6-13. doi: 10.5114/wo.2013.33766. Epub 2013 Mar 15.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Očekávaný)
Primární dokončení (Očekávaný)
Dokončení studie (Očekávaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Koronavirové infekce
- Infekce Coronaviridae
- Infekce Nidovirales
- RNA virové infekce
- Virová onemocnění
- Infekce
- Infekce dýchacích cest
- Nemoci dýchacích cest
- Pneumonie, virová
- Zápal plic
- Plicní onemocnění
- COVID-19
- Molekulární mechanismy farmakologického působení
- Fibrinolytická činidla
- Činidla modulující fibrin
- Antikoagulancia
- Heparin s nízkou molekulovou hmotností
- Tinzaparin
- Dalteparin
Další identifikační čísla studie
- 18634/23-7-2021 pend. aprooval
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