This is a multicenter, randomized, open-label, assessor-blind, event-driven, non-inferiority program for efficacy with a study treatment duration of 3, 6 or 12 months in patients with confirmed acute symptomatic DVT without symptomatic PE (Einstein-DVT).
CONTEXTE: Le rivaroxaban, un inhibiteur oral du facteur Xa, peut fournir un moyen simple, à dose fixe pour le traitement aigu régime de la thrombose veineuse profonde (TVP) et d'un traitement continu, sans la nécessité d'une surveillance en laboratoire.
MÉTHODES: Nous avons mené une étude ouverte, randomisée, event-driven étude de non-infériorité, que par rapport rivaroxaban par voie orale seule (15 mg deux fois par jour pendant 3 semaines, puis 20 mg une fois par jour) avec énoxaparine sous-cutanée suivie d'un antagoniste de la vitamine K (soit la warfarine ou acénocoumarol) pendant 3, 6 ou 12 mois chez les patients en phase aiguë, thrombose veineuse profonde symptomatique. En parallèle, nous avons mené une double-aveugle, randomisée, étude de supériorité event-driven qui a comparé le rivaroxaban seul (20 mg une fois par jour) à un placebo pendant 6 ou 12 mois supplémentaires chez les patients ayant terminé 6 à 12 mois de traitement pour veineux thrombo-embolie. Le critère principal d'efficacité pour les deux études était la thromboembolie veineuse récurrente. Le résultat principal de sécurité était saignements majeurs ou des saignements cliniquement pertinente nonmajor dans l'étude initiale de traitement et les saignements majeurs dans l'étude de la poursuite du traitement-.
RÉSULTATS: L'étude du rivaroxaban pour la TVP aiguë inclus 3449 patients: 1731 rivaroxaban donnée et 1718 énoxaparine donné plus un antagoniste de la vitamine K. Le rivaroxaban a une efficacité non inférieure par rapport à l'issue primaire (36 événements [2,1%], contre 51 événements avec l'énoxaparine, anti-vitamine K [3,0%]; hazard ratio: 0,68; intervalle de confiance 95% [IC]: 0,44 à 1,04; P <0,001). Le résultat principal de sécurité s'est produite chez 8,1% des patients dans chaque groupe. Dans l'étude de la poursuite du traitement, qui comprenait 602 patients dans le groupe rivaroxaban et 594 dans le groupe placebo, le rivaroxaban a eu une efficacité supérieure (8 événements [1,3%], contre 42 avec le placebo [7,1%]; hazard ratio: 0,18; 95 % IC, 0,09 à 0,39, P <0,001). Quatre patients dans le groupe rivaroxaban eu des saignements majeurs non fatals (0,7%), contre aucun dans le groupe placebo (P = 0,11).
CONCLUSIONS: Le rivaroxaban offre une solution simple, un seul médicament approche pour le traitement à court terme et la poursuite de la thrombose veineuse qui peut améliorer le profil bénéfice-risque du traitement anticoagulant. (Financé par Bayer Schering Pharma et Ortho-McNeil;. Numéros ClinicalTrials.gov, NCT00440193 NCT00439725 et).
Rivaroxaban, an oral, direct factor Xa inhibitor, has been approved for the treatment of deep-vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention of recurrent DVT and PE as a fixed-dose, single-drug regimen that does not require initial heparinisation, routine coagulation monitoring or dose adjustment. This study evaluated patient-reported treatment satisfaction in EINSTEIN DVT--a large, open-label, randomised study that compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy in patients with acute symptomatic DVT without PE. As part of EINSTEIN DVT, a total of 1,472 patients in seven countries were asked to complete a new, validated measure of treatment satisfaction--the Anti-Clot Treatment Scale (ACTS)--at scheduled visits throughout 12 months of treatment. ACTS scores were compared between study groups in the intention-to-treat population. Patients reported greater satisfaction in the rivaroxaban group compared with the enoxaparin/VKA group, with higher mean ACTS scores across visits. Mean ACTS Burdens scores were 55.2 vs 52.6 (p<0.0001) in favour of rivaroxaban, equivalent to a moderate effect size of 0.42. The treatment effect was consistent over time, with the mean score difference ranging from 2.18 (month 2) to 3.18 (month 12). Overall mean ACTS Benefits scores were 11.7 vs 11.5 in favour of rivaroxaban (p=0.006). This was associated with a small overall effect size of 0.12. The improvement in ACTS Benefits for rivaroxaban became apparent at month 2 and subsequent visits. Rivaroxaban results in improved treatment satisfaction compared with enoxaparin/VKA among patients with DVT, particularly in reducing patient-reported anticoagulation burden.
Background: Patients with venous thromboembolism and cancer have a substantial risk of recurrent venous thromboembolism and bleeding during anticoagulant therapy. Although monotherapy with low-molecular-weight heparin is recommended in these patients, in clinical practice many patients with venous thromboembolism and cancer do not receive this treatment. We aimed to assess the efficacy and safety of a single-drug regimen with oral rivaroxaban compared with enoxaparin followed by vitamin K antagonists, in the subgroup of patients with cancer enrolled in the EINSTEIN-DVT and EINSTEIN-PE randomised controlled trials. Methods: We did a subgroup analysis of patients with active cancer (either at baseline or diagnosed during the study), a history of cancer, or no cancer who were enrolled in the EINSTEIN-DVT and EINSTEIN-PE trials. Eligible patients with deep-vein thrombosis (EINSTEIN-DVT) or pulmonary embolism (EINSTEIN-PE) were randomly assigned in a 1:1 ratio to receive rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily) or standard therapy (enoxaparin 1·0 mg/kg twice daily and warfarin or acenocoumarol; international normalised ratio 2·0-3·0). Randomisation with a computerised voice-response system was stratified according to country and intended treatment duration (3, 6, or 12 months). The prespecified primary efficacy and safety outcomes of both the trials and this subanalysis were symptomatic recurrent venous thromboembolism and clinically relevant bleeding, respectively. We did efficacy and mortality analyses in the intention-to-treat population, and bleeding analyses for time spent receiving treatment plus 2 days in the safety population (all patients who received at least one dose of study drug). The EINSTEIN-DVT and EINSTEIN-PE studies are registered at ClinicalTrials.gov, numbers NCT00440193 and NCT00439777. Findings: In patients with active cancer (diagnosed at baseline or during treatment), recurrent venous thromboembolism occurred in 16 (5%) of 354 patients allocated to rivaroxaban and 20 (7%) of 301 patients allocated to enoxaparin and vitamin K antagonist (hazard ratio [HR] 0·67, 95% CI 0·35 to 1·30). Clinically relevant bleeding occurred in 48 (14%) of 353 patients receiving rivaroxaban and in 49 (16%) of 298 patients receiving standard therapy (HR 0·80, 95% CI 0·54 to 1·20). Major bleeding occurred in eight (2%) of 353 patients receiving rivaroxaban and in 15 (5%) of 298 patients receiving standard therapy (HR 0·42, 95% CI 0·18 to 0·99). The overall frequency of recurrent venous thromboembolism in patients with only a history of cancer (five [2%] of 233 patients in the rivaroxaban group vs five [2%] of 236 in the standard therapy group; HR 0·98, 95% CI 0·28-3·43) was similar to that of patients without cancer (65 [2%] of 3563 vs 70 [2%] of 3594, respectively; HR 0·93, 95% CI 0·66-1·30), but the frequency was increased in patients with active cancer at baseline (six [2%] of 258 vs eight [4%] of 204, respectively; HR 0·62, 95% CI 0·21-1·79) and most markedly increased in patients whose diagnosis of cancer was made during the study (ten [10%] of 96 vs 12 [12%] of 97, respectively; HR 0·80, 95% CI 0·34-1·88). The overall frequency of major bleeding in patients with only a history of cancer (one [<1%] patient in the rivaroxaban group vs four [2%] patients in the standard therapy group; HR 0·23, 95% CI 0·03-2·06) was similar to that of patients without cancer (31 [1%] vs 53 [1%], respectively; HR 0·58, 95% CI 0·37-0·91), but was increased in patients with active cancer at baseline (five [2%] vs eight [4%], respectively; HR 0·47, 95% CI 0·15-1·45) and was highest in those with cancer diagnosed during the study (three [3%] vs seven [7%], respectively; HR 0·33, 95% CI 0·08-1·31). Interpretation: In patients with active cancer and venous thromboembolism, rivaroxaban had similar efficacy to prevent recurrence of venous thromboembolism and reduced the number major bleeding events compared with treatment with enoxaparin and a vitamin K antagonist, although there was no difference between groups for clinically relevant bleeding. Based on these results, a head-to-head comparison of rivaroxaban with long-term low-molecularweight heparin in patients with cancer is warranted.
This is a multicenter, randomized, open-label, assessor-blind, event-driven, non-inferiority program for efficacy with a study treatment duration of 3, 6 or 12 months in patients with confirmed acute symptomatic DVT without symptomatic PE (Einstein-DVT).
Devis de recherche»Essai contrôlé randomisé (ECR)
Pays»Australia,Austria,Belgium,Brazil,Canada,China,Czech Republic,Denmark,Finland,France,Germany,Hong Kong,Hungary,India,Indonesia,Israel,Italy,Korea, Republic of,Malaysia,Netherlands,New Zealand,Norway,Philippines,Poland,Puerto Rico,Singapore,South Africa,Spain,Sweden,Switzerland,Thailand,United Kingdom,United States
