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.Me… Show more
“…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.…”
Section: Methodsmentioning
confidence: 99%
“…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 …”
Section: Methodsmentioning
confidence: 99%
“…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.…”
Section: Designmentioning
confidence: 99%
“…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.…”
Section: Inclusion and Exclusion Criteriamentioning
Background
Randomized controlled trials showed the nonvitamin K oral anticoagulant (NOAC) edoxaban was effective and safe for stroke and systemic embolism prevention in nonvalvular atrial fibrillation (AF) and for the prevention and treatment of venous thromboembolism (VTE; including pulmonary embolism and deep vein thrombosis). Additional research is needed to evaluate the effects of edoxaban in routine clinical practice. Therefore, the Edoxaban Treatment in routine cliNical prActice (ETNA) program is being conducted to provide routine clinical care data on characteristics and outcomes in patients with AF or VTE receiving edoxaban.
Methods
The Global ETNA program integrates prospectively collected data from edoxaban patients in regional ETNA noninterventional studies across Europe, Japan, and East and Southeast Asia into indication‐specific databases for AF and VTE. Targeted enrollment is >31 000 patients (AF >26 000; VTE >4500), with a follow‐up of 2 years for AF and 1 year for VTE. Data integration will be possible using consistent terminology, parameter definitions, and data collection across the regional noninterventional studies. Safety and effectiveness data will be assessed. Crude rates of outcomes including bleeding and thromboembolic events will be reported.
Results
Globally, enrollment began in early 2015 and is ongoing.
Conclusions
Global ETNA will generate the largest integrated prospective repository of routine clinical care data for a single NOAC in patients with AF or VTE. It will provide important information on the safety of edoxaban in routine clinical care and gather further information on its effectiveness.
“…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.…”
Section: Methodsmentioning
confidence: 99%
“…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 …”
Section: Methodsmentioning
confidence: 99%
“…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.…”
Section: Designmentioning
confidence: 99%
“…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.…”
Section: Inclusion and Exclusion Criteriamentioning
Background
Randomized controlled trials showed the nonvitamin K oral anticoagulant (NOAC) edoxaban was effective and safe for stroke and systemic embolism prevention in nonvalvular atrial fibrillation (AF) and for the prevention and treatment of venous thromboembolism (VTE; including pulmonary embolism and deep vein thrombosis). Additional research is needed to evaluate the effects of edoxaban in routine clinical practice. Therefore, the Edoxaban Treatment in routine cliNical prActice (ETNA) program is being conducted to provide routine clinical care data on characteristics and outcomes in patients with AF or VTE receiving edoxaban.
Methods
The Global ETNA program integrates prospectively collected data from edoxaban patients in regional ETNA noninterventional studies across Europe, Japan, and East and Southeast Asia into indication‐specific databases for AF and VTE. Targeted enrollment is >31 000 patients (AF >26 000; VTE >4500), with a follow‐up of 2 years for AF and 1 year for VTE. Data integration will be possible using consistent terminology, parameter definitions, and data collection across the regional noninterventional studies. Safety and effectiveness data will be assessed. Crude rates of outcomes including bleeding and thromboembolic events will be reported.
Results
Globally, enrollment began in early 2015 and is ongoing.
Conclusions
Global ETNA will generate the largest integrated prospective repository of routine clinical care data for a single NOAC in patients with AF or VTE. It will provide important information on the safety of edoxaban in routine clinical care and gather further information on its effectiveness.
“…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.…”
Edoxaban is used for venous thromboembolism (VTE) treatment. Real-life data are lacking about its use in long-term therapy. We aimed to assess the efficacy and the safety of edoxaban for long-term VTE treatment in a real-life setting. Patients with VTE included in the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry, receiving edoxaban 60 or 30 mg daily were prospectively followed up to validate the benefit of using different dosages. The main outcome was the composite of VTE recurrences or major bleeding in patients with or without criteria for dose reduction. Multivariable analysis to identify predictors for the composite outcome was performed. From October 2015 to November 2019, 562 patients received edoxaban for long-term therapy. Most (94%) of the 416 patients not meeting criteria for dose reduction received 60 mg daily, and 92 patients meeting criteria (63%) received 30 mg daily. During treatment, two patients developed recurrent VTE, six had major bleeding and nine died (2 from fatal bleeding). Among patients not meeting criteria for dose reduction, those receiving 30 mg daily had a higher rate of the composite event (hazard ratio (HR) 8.37; 95% confidence interval (CI) 1.12-42.4) and a significant higher mortality rate (HR 31.1; 95% CI 4.63-262) than those receiving 60 mg. Among patients meeting criteria for dose reduction, those receiving 60 mg daily had no events, and a nonsignificantly higher mortality rate (HR 5.04; 95% CI 0.54-133) than those receiving 30 mg daily. In conclusion, edoxaban seems to be effective and safe for long-term VTE treatment in real life. Criteria for dose reduction should be reformulated. Current guidelines of antithrombotic therapy, 1,2 based on the evidence from randomized trials, 3-7 recommend the use of direct oral anticoagulants (DOACs) as initial and long-term therapy in patients with venous thromboembolism (VTE). However, the pivotal trials where their indication was based applied strict exclusion criteria, aimed to exclude patients with a presumed high risk of bleeding. The International Regulatory Authorities encourage the pharmaceutical companies to develop postauthorization safety studies that should start shortly after the approval of the
Background
Postthrombotic syndrome (PTS) is a long‐term complication after deep vein thrombosis (DVT) and can affect quality of life (QoL). Pathogenesis is not fully understood but inadequate anticoagulant therapy with vitamin K antagonists is a known risk factor for the development of PTS.
Objectives
To compare the prevalence of PTS after acute DVT and the long‐term QoL following DVT between patients treated with edoxaban or warfarin.
Methods
We performed a long‐term follow‐up study in a subset of patients with DVT who participated in the Hokusai‐VTE trial between 2010 and 2012 (NCT00986154). Primary outcome was the prevalence of PTS, defined by the Villalta score. The secondary outcome was QoL, assessed by validated disease‐specific (VEINES‐QOL) and generic health‐related (SF‐36) questionnaires.
Results
Between 2017 and 2020, 316 patients were enrolled in 26 centers in eight countries, of which 168 (53%) patients had been assigned to edoxaban and 148 (47%) to warfarin during the Hokusai‐VTE trial. Clinical, demographic, and thrombus‐specific characteristics were comparable for both groups. Mean (SD) time since randomization in the Hokusai‐VTE trial was 7.0 (1.0) years. PTS was diagnosed in 85 (51%) patients treated with edoxaban and 62 (42%) patients treated with warfarin (adjusted odds ratio 1.6, 95% CI 1.0–2.6). Mean differences in QoL scores between treatment groups were not clinically relevant.
Conclusion
Contrary to our hypothesis, the prevalence of PTS tended to be higher in patients treated with edoxaban compared with warfarin. No differences in QoL were observed. Further research is warranted to unravel the role of anticoagulant therapy on development of PTS.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.