Design and rationale of the non-interventional, edoxaban treatment in routiNe clinical prActice in patients with venous ThromboEmbolism in Europe (ETNA-VTE-Europe) study

Alexander T Cohen, Cihan Ay, Philippe Hainaut, Hervé Décousus, Ulrich Hoffmann, Sean Gaine, Michiel Coppens, Pedro Marques da Silva, David Jimenez Castro, Beatrice Amann-Vesti, Bernd Brüggenjürgen, Pierre Levy, Julio Lopez Bastida, Eric Vicaut, Petra Laeis, Eva-Maria Fronk, Wolfgang Zierhut, Thomas Malzer, Peter Bramlage, Giancarlo Agnelli, ETNA-VTE-Europe investigators, Alexander T Cohen, Cihan Ay, Philippe Hainaut, Hervé Décousus, Ulrich Hoffmann, Sean Gaine, Michiel Coppens, Pedro Marques da Silva, David Jimenez Castro, Beatrice Amann-Vesti, Bernd Brüggenjürgen, Pierre Levy, Julio Lopez Bastida, Eric Vicaut, Petra Laeis, Eva-Maria Fronk, Wolfgang Zierhut, Thomas Malzer, Peter Bramlage, Giancarlo Agnelli, ETNA-VTE-Europe investigators

Abstract

Background: Venous thromboembolism (VTE, including deep vein thrombosis [DVT] and pulmonary embolism [PE]) has an annual incidence rate of 104-183 per 100,000 person-years. After a VTE episode, the two-year recurrence rate is about 17%. Consequently, effective and safe anticoagulation is paramount. Edoxaban is a direct oral anticoagulant (DOAC) approved VTE treatment. Current safety and efficacy data are derived from clinical trials, and information about treatment durations beyond 12 months are not available.

Methods: ETNA-VTE-Europe is an 18-month prospective, single-arm, non-interventional, multinational post-authorisation safety study. Approximately 310 sites across eight European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Switzerland and the United Kingdom) will participate in the study, with the intention to represent the regional distributions of centres, healthcare settings and specialties. An estimated cohort of 2700 patients will be recruited, the only enrolment criteria being acute symptomatic VTE, no participation in an interventional study, and treating physician decision to prescribe edoxaban independently from the registry. Data from patient medical records and/or telephone interviews will be collected at baseline, 1, 3, 6, 12 and 18 months. The primary objective is to evaluate the 18-month rate of symptomatic VTE recurrence in patients with VTE treated with edoxaban outside a clinical trial. The co-primary objective is to evaluate the real-world rates of bleeding and adverse drug reactions. Secondary outcomes include rates of other patient-relevant safety events, adherence to and discontinuation of edoxaban. Furthermore, 12-month ETNA-VTE-Europe data will be considered in the context of those for patients receiving different anticoagulants in the PREFER in VTE registry and Hokusai-VTE clinical trial.

Conclusions: ETNA-VTE-Europe will allow the safety and effectiveness of edoxaban to be evaluated over an extended period in acute symptomatic VTE patients encountered in routine clinical practice. Findings will be informative for European practitioners prescribing edoxaban as part of real-world VTE treatment/prevention.

Trial registration: ClinicalTrials.gov Identifier: NCT02943993.

Keywords: Anticoagulation; Direct oral anticoagulant (DOAC/NOAC); Edoxaban; Registry; Venous thromboembolism (VTE).

Conflict of interest statement

Approval from the responsible ethics committees and institutional review boards will be obtained prior to protocol implementation. Informed consent will be obtained from all patients prior to enrolment and compliance with the Declaration of Helsinki will be ensured throughout the study.Not applicable.The members of the Steering Committee received honoraria for their advice in the planning of the Registry. They also received honoraria and travel reimbursements from Daiichi Sankyo Europe GmbH for their participation in Steering Committee Meetings. Alexander T. Cohen, Hervé Décousus, Pedro Marques da Silva, David Jimenez Castro, Beatrice Amann-Vesti, Bernd Brüggenjürgen, Eric Vicaut and Giancarlo Agnelli have received research support and/or honoraria for lectures from a number of pharmaceutical companies including Daiichi Sankyo, the sponsor of the registry. Cihan Ay received honoraria for lectures from Sanofi, Pfizer/BMS, Daiichi-Sankyo, Boehringer Ingelheim, and Bayer. Advisory board membership for Pfizer/BMS, Daiichi-Sankyo, Boehringer Ingelheim, and Bayer. Philippe Hainaut received honoraria from Daiichi Sankyo Europe GmbH for lectures and advisory board membership. Ulrich Hoffmann received honoraria for lectures from Bayer, Daiichi-Sankyo, Leo Pharma, Pfizer, Bristol-Meyers, Aspen, Sanofi-Aventis, Amgen. Advisory board membership for Bayer, Daiichi-Sankyo, Leo Pharma, Sanofi-Aventis, and Amgen. Sean Gaine received honoraria for lectures from Actelion Pharmaceuticals Ltd., Bayer, GlaxoSmithKline, Merck Sharpe & Dohme, and has received advisory and/or drug safety board fees from Astra Zeneca, Actelion Pharmaceuticals Ltd., Bayer, GlaxoSmithKline, Novartis, Pfizer and Daiichi-Sankyo, Menerini, and United Therapeutics. Michiel Coppens has received research funding and honoraria for consultancy or lecturing from Daiichi Sankyo, Boehringer Ingelheim, Bayer, Bristol-Myers Squibb and Pfizer. Pierre Levy received honoraria for lectures from AbbVie, Amgen, Gilead, GSK, Novo Nordisk, ViiV. Advisory board membership for AbbVie, Actelion, Amgen, Astellas, Bayer, Biogen, Boehringer Ingelheim, Celgène, Daiichi Sankyo, Eli Lilly, EOS, GSK, Janssen, MSD, Mundipharma, Novartis, Pfizer, Roche, Shire, Vertex. Julio Lopez Bastida received honoraria from Daiichi Sankyo. Petra Laeis, Eva-Maria Fronk, Wolfgang Zierhut, and Thomas Malzer are employees of Daiichi Sankyo Europe GmbH. Peter Bramlage received research funding and consultancy honoraria from Daiichi Sankyo Europe GmbH. He further received funding for drafting the manuscript. The members of the Steering Committee received honoraria and travel reimbursements from Daiichi Sankyo Europe GmbH for their participation in Steering Committee Meetings.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

    1. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol. 2015;12:464–474. doi: 10.1038/nrcardio.2015.83.
    1. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet. 2012;379:1835–1846. doi: 10.1016/S0140-6736(11)61904-1.
    1. Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P, Folsom AR. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19–25. doi: 10.1016/j.amjmed.2004.01.018.
    1. Heit JA. Predicting the risk of venous thromboembolism recurrence. Am J Hematol. 2012;87(Suppl 1):S63–S67. doi: 10.1002/ajh.23128.
    1. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–2104. doi: 10.1056/NEJMoa1310907.
    1. Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406–1415. doi: 10.1056/NEJMoa1306638.
    1. Lixiana (edoxaban): Summary of Product Characteristics []. Accessed 2017.
    1. Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, Gibbs JS, Huisman MV, Humbert M, Kucher N, et al: 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014, 35:3033–3069, 3069a-3069k.
    1. Summary of the risk management plan (RMP) for Lixiana (edoxaban) []. Accessed 2017.
    1. Edoxaban Treatment in Routine Clinical Practice for Patients With Non Valvular Atrial Fibrillation (ETNA-AF-EU: NCT02944019) []. Accessed 2017.
    1. Schulman S, Kearon C, the SOCOAOTS, Standardization Committee Of The International Society On T, Haemostasis Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3:692–694. doi: 10.1111/j.1538-7836.2005.01204.x.
    1. Investigators TH-V. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406–1415. doi: 10.1056/NEJMoa1306638.
    1. Cohen AT, Gitt AK, Bauersachs R, Fronk EM, Laeis P, Mismetti P, Monreal M, Willich SN, Bramlage P, Agnelli G, et al. The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE registry. Thromb Haemost. 2017;117:1326–1337. doi: 10.1160/TH16-10-0793.
    1. Agnelli G, Gitt AK, Bauersachs R, Fronk EM, Laeis P, Mismetti P, Monreal M, Willich SN, Wolf WP, Cohen AT. The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE registry. Thromb J. 2015;13:41. doi: 10.1186/s12959-015-0071-z.
    1. Raskob G, Buller H, Prins M, Segers A, Shi M, Schwocho L, van Kranen R, Mercuri M. Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-venous thromboembolism study--methodological implications for clinical trials. J Thromb Haemost. 2013;11:1287–1294. doi: 10.1111/jth.12230.
    1. Guideline on good pharmacovigilance practices (GVP) Module VI – Management and reporting of adverse reactions to medicinal products (Rev 1) []. Accessed 2017.
    1. Public Policy Committee ISoP Guidelines for good pharmacoepidemiology practice (GPP) Pharmacoepidemiol Drug Saf. 2016;25:2–10. doi: 10.1002/pds.3891.
    1. Verso M, Agnelli G, Ageno W, Imberti D, Moia M, Palareti G, Pistelli R, Cantone V. Long-term death and recurrence in patients with acute venous thromboembolism: the MASTER registry. Thromb Res. 2012;130:369–373. doi: 10.1016/j.thromres.2012.04.003.
    1. Spirk D, Ugi J, Korte W, Husmann M, Hayoz D, Baldi T, Frauchiger B, Banyai M, Aujesky D, Baumgartner I, Kucher N. Long-term anticoagulation treatment for acute venous thromboembolism in patients with and without cancer. The SWIss venous ThromboEmbolism registry (SWIVTER) II. Thromb Haemost. 2011;105:962–967. doi: 10.1160/TH11-01-0002.
    1. Weitz JI, Haas S, Ageno W, Angchaisuksiri P, Bounameaux H, Nielsen JD, Goldhaber SZ, Goto S, Kayani G, Mantovani L, et al. Global anticoagulant registry in the field - venous thromboembolism (GARFIELD-VTE). Rationale and design. Thromb Haemost. 2016;116:1172–1179. doi: 10.1160/TH16-04-0335.
    1. Monreal M, Suarez C, Fajardo JA, Barba R, Uresandi F, Valle R, Rondon P. Management of patients with acute venous thromboembolism: findings from the RIETE registry. Pathophysiol Haemost Thromb. 2003;33:330–334. doi: 10.1159/000083823.
    1. Ageno W, Mantovani LG, Haas S, Kreutz R, Monje D, Schneider J, van Eickels M, Gebel M, Zell E, Turpie AG. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol. 2016;3:e12–e21. doi: 10.1016/S2352-3026(15)00257-4.
    1. Ageno W, Casella IB, Han CK, Raskob GE, Schellong S, Schulman S, Singer DE, Kimura K, Tang W, Desch M, Goldhaber SZ, RE-COVERY DVT. PE: rationale and design of a prospective observational study of acute venous thromboembolism with a focus on dabigatran etexilate. Thromb Haemost. 2017;117:415–421. doi: 10.1160/TH16-07-0566.
    1. Ageno W, Mantovani LG, Haas S, Kreutz R, Haupt V, Schneider J, Turpie AG. XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis. Thromb J. 2014;12:16. doi: 10.1186/1477-9560-12-16.
    1. About GARFIELD-VTE []. Accessed 2017.
    1. RE-COVERY DVT/PE: Global Study on Treatment Secondary Prevention of Acute Venous Thromboembolism. .

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