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

Abstract

BackgroundVenous 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.MethodsETNA-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.ConclusionsETNA-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 registrationClinicalTrials.gov Identifier: NCT02943993.

The global Edoxaban Treatment in routine cliNical prActice (ETNA) noninterventional study program: rationale and design

“…Power analyses for sample size justification were performed on a regional basis. Detailed sample size justification for ETNA‐AF and ETNA‐VTE Europe has been published previously . In ETNA‐AF Japan, a total of 10 000 patients will be enrolled.…”

“…For ETNA‐VTE, eligible patients are those diagnosed with initial or recurrent acute VTE and treated with edoxaban according to the local label. Patients enrolled in ETNA‐VTE Europe were only eligible if the diagnosis of initial or recurrent acute VTE occurred no more than 2 weeks prior to enrollment …”

“…Detailed sample size justification for ETNA-AF and ETNA-VTE Europe has been published previously. 6,7 In ETNA-AF Japan, a total of 10 000 patients will be enrolled. Based on the interim analysis of a postmarketing surveillance of another new orally active anticoagulant, 2% of patients enrolled are expected to have severe renal impairment.…”

“…Patients enrolled in ETNA-VTE Europe were only eligible if the diagnosis of initial or recurrent acute VTE occurred no more than 2 weeks prior to enrollment. 7 Due to the noninterventional design, the only exclusion criteria are not providing written informed consent or participating in a simultaneous interventional study.…”

Edoxaban for the Long‐Term Therapy of Venous Thromboembolism: Should the Criteria for Dose Reduction be Revised?

“…Two postauthorization safety studies have been commissioned by the EMA, but conclusive data are not yet available. 12,13 In the current study, we used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE), a prospective multinational registry of patients with objectively confirmed VTE (ClinicalTrials.gov identifier: NCT02832245), to assess the efficacy and safety of edoxaban for long-term therapy of VTE in real-life clinical practice. 14,15 According to the product label, the recommended dose of edoxaban for long-term therapy is 60 mg daily, but this dose should be reduced to 30 mg daily in patients with creatinine clearance (CrCl) levels 15-50 mL/minute, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors, because they are perceived as being at increased risk for bleeding.…”