Intensive Dose Tinzaparin in Hospitalized COVID-19 Patients (INTERACT)
Intensive Dose Tinzaparin in Hospitalized COVID19 Patients
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Voraussichtlich)
Kontakte und Standorte
Studienkontakt
- Name: Karolina Akinosoglou, MD,PhD
- Telefonnummer: +306977762897
- E-Mail: akin@upatras.gr
Studienorte
-
-
Achaia
-
Patras, Achaia, Griechenland, 26504
- Rekrutierung
- University Hospital of Patras
-
Kontakt:
- Karolina Akinosoglou, Ass. Prof.
- Telefonnummer: +30 2610997254
- E-Mail: akin@upatras.gr
-
-
Attica
-
Athens, Attica, Griechenland, 10676
- Rekrutierung
- Evangelismos General Hospital
-
Kontakt:
- George Marakomichelakis, M.D. Ph.D.
-
Unterermittler:
- Christine Vadala, M.D. Ph.D.
-
Athens, Attica, Griechenland, 11522
- Rekrutierung
- General Hopital Elpis
-
Kontakt:
- Spyridon Savvanis, M.D. Ph.D
-
-
Epirus
-
Ioannina, Epirus, Griechenland, 45500
- Rekrutierung
- University General Hospital Of Ioannina
-
Kontakt:
- Haralampos ] Milionis, Ass. Prof.
-
-
Ionian Islands
-
Korfu, Ionian Islands, Griechenland, 49100
- Rekrutierung
- General Hospital of Kerkira "Ag. Irini"
-
Kontakt:
- Ilias Papanicolaou, M.D. Ph.D.
-
-
Macedonia
-
Kozáni, Macedonia, Griechenland, 50100
- Rekrutierung
- General Hospital of Kozani "Mamatsio"
-
Kontakt:
- Efthalia Randou, M.D. Ph.D.
-
-
Peloponnese
-
Patras, Peloponnese, Griechenland, 26335
- Rekrutierung
- Genereal Hospital of Patras "Ag. Andreas"
-
Kontakt:
- George Efremidis, M.D. Ph.D.
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Probenahmeverfahren
Studienpopulation
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
Kohorten und Interventionen
Gruppe / Kohorte |
Intervention / Behandlung |
|---|---|
|
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
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Incidence of thrombotic events
Zeitfenster: 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
Zeitfenster: 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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
WHO progression scale
Zeitfenster: 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
Zeitfenster: through study completion, an average of 6 months
|
Evaluate the length of hospital stay (in days)
|
through study completion, an average of 6 months
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Karolina Akinosoglou, MD,PhD, University Hospital of Patras
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- 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.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Voraussichtlich)
Primärer Abschluss (Voraussichtlich)
Studienabschluss (Voraussichtlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Coronavirus-Infektionen
- Coronaviridae-Infektionen
- Nidovirales-Infektionen
- RNA-Virusinfektionen
- Viruserkrankungen
- Infektionen
- Infektionen der Atemwege
- Erkrankungen der Atemwege
- Pneumonie, viral
- Lungenentzündung
- Lungenkrankheit
- COVID-19
- Molekulare Mechanismen der pharmakologischen Wirkung
- Fibrinolytische Mittel
- Fibrinmodulierende Mittel
- Antikoagulanzien
- Heparin, niedermolekular
- Tinzaparin
- Dalteparin
Andere Studien-ID-Nummern
- 18634/23-7-2021 pend. aprooval
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Produkt, das in den USA hergestellt und aus den USA exportiert wird
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .