The primary objective of the trial is to demonstrate non-inferiority of 220 mg oral dabigatran etexilate compared to 40 mg subcutaneous enoxaparin administered once daily. Safety and efficacy will be compared between the treatment groups.
BACKGROUND: Extended thromboprophylaxis after hip arthroplasty reduces the risk of venous thromboembolism (VTE). As oral dabigatran offers practical advantages over subcutaneous enoxaparin in the post-discharge setting, we compared the efficacy and safety of these treatments in this indication. METHODS: In this double-blind, non-inferiority trial, 2055 patients undergoing total hip arthroplasty were randomized to treatment for 28 to 35 days with oral dabigatran, 220 mg once-daily, starting with a half-dose 1 to 4 hours after surgery, or subcutaneous enoxaparin 40 mg once-daily, starting the evening before surgery. The primary efficacy outcome was a composite of total VTE (venographic or symptomatic) and death from all-causes. The main secondary composite outcome was major VTE (proximal deep-vein thrombosis, nonfatal pulmonary embolism) plus VTE-related death. The main safety outcome was major bleeding during treatment. RESULTS: The median treatment duration was 32 days. In total, 2013 were treated, of whom 1577 operated patients were included in the primary efficacy analysis. The primary efficacy outcome occurred in 7.7% (61 of 792) of the dabigatran group versus 8.8% (69 of 785) of the enoxaparin group, absolute risk difference -1.1% (95% confidence interval [CI], -3.8 to 1.6%); P<0.0001 for the pre-specified non-inferiority margin. The main secondary efficacy outcome occurred in 2.2% (18 of 805) of the dabigatran group versus 4.2% (33 of 794) of the enoxaparin group (absolute risk difference -1.9%, (95% CI,-3.6% to -0.2%; P=0.03). Major bleeding occurred in 1.4% of the dabigatran group and 0.9% of the enoxaparin group (P=0.40). The incidence of adverse events during treatment did not differ significantly between the groups. CONCLUSIONS: Extended prophylaxis with oral dabigatran 220 mg once-daily was as effective as subcutaneous enoxaparin 40 mg once-daily in reducing the risk of VTE after total hip arthroplasty. The risk of bleeding and safety profiles were similar.
Cette étude a comparé l'efficacité et la sécurité de dabigatran orale, un inhibiteur direct de la thrombine, par rapport à l'énoxaparine sous-cutanée pour une thromboprophylaxie prolongée chez les patients subissant une arthroplastie totale de la hanche. Un total de 2055 patients ont été randomisés pour 28-35 jours de traitement par voie orale de dabigatran, 220 mg une fois par jour, à commencer par une demi-dose 1-4 heures après la chirurgie, ou énoxaparine sous-cutanée de 40 mg une fois par jour, en commençant la veille de la chirurgie . Le critère principal d'efficacité était un critère composite de la thromboembolie veineuse totale [VTE] (phlébographie ou symptomatique) et la mort de toutes causes. Le principal critère secondaire composite était important TEV (proximale thrombose veineuse profonde ou non mortelles embolie pulmonaire), plus décès liés aux TVP. Le résultat principal était la sécurité des saignements majeurs. Au total, 2.013 ont été traités, dont 1.577 patients opérés ont été inclus dans l'analyse d'efficacité primaire. Le critère d'efficacité principal a été observé chez 7,7% dans le groupe dabigatran contre 8,8% dans le groupe énoxaparine, la différence de risque (DR) -1,1% (IC à 95% -3,8 à 1,6%), p <0,0001 pour la pré-spécifiée de non-infériorité la marge. TEV majeure et liés aux ETEV décès est survenu chez 2,2% dans le groupe dabigatran versus 4,2% dans le groupe énoxaparine, RD -1,9% (-3,6% à -0,2%), p = 0,03. Saignements majeurs chez 1,4% dans le groupe dabigatran et de 0,9% dans le groupe énoxaparine (p = 0,40). L'incidence des événements indésirables, y compris les élévations des enzymes hépatiques et des événements cardiaques, au cours du traitement était similaire entre les groupes. Prophylaxie prolongée par voie orale 220 mg de dabigatran une fois par jour était aussi efficace que l'énoxaparine sous-cutanée de 40 mg une fois par jour pour réduire le risque de TEV après une arthroplastie totale de la hanche, et supérieur à l'énoxaparine pour réduire le risque de TEV majeure. Le risque de saignement et des profils d'innocuité étaient semblables.
OBJECTIVE: In the Re-NOVATE II study, oral dabigatran provided thromboprophylaxis after total hip arthroplasty and improved compliance postdischarge in a global population. This article aims to identify trends (if any) in the Indian population.
METHODS: In this prospective, double-blind, double-dummy study, patients scheduled for primary, unilateral, elective total hip arthroplasty were randomized to 220 mg oral dabigatran once daily, starting with a 110 mg half-dose, 1-4 hours after surgery, or subcutaneous enoxaparin 40 mg once daily, starting the evening before surgery. Each group received a placebo of the other study drug. The primary efficacy outcome was the composite of total venous thromboembolism (VTE) and all-cause mortality. Secondary outcome measures were composite of major VTE and VTE-related mortality during the treatment period. The major safety outcome was incidence of bleeding events.
RESULTS: Of the 179 Indian patients randomized, 91 received oral dabigatran and 88 received subcutaneous enoxaparin for 28-35 days. Total VTE and all-cause mortality occurred in 18.7% of patients in the dabigatran group and 13.7% in the enoxaparin group [odds ratio = 1.4 (95% confidence interval 0.6, 3.5)]. Major VTE and VTE-related mortality was numerically lower in the dabigatran group (7.9%) compared with the enoxaparin group (9.9%). Safety outcomes were comparable between both groups.
CONCLUSION: Dabigatran is an effective oral alternative to enoxaparin for thromboprophylaxis as demonstrated by the RE-NOVATE II study global results. Data analyzed in Indian patients indicate comparable effects of dabigatran etexilate for major efficacy and safety outcomes.
The primary objective of the trial is to demonstrate non-inferiority of 220 mg oral dabigatran etexilate compared to 40 mg subcutaneous enoxaparin administered once daily. Safety and efficacy will be compared between the treatment groups.
Devis de recherche»Essai contrôlé randomisé (ECR)
Pays»Australia,Austria,Belgium,Canada,Czech Republic,Denmark,Finland,Germany,Hungary,India,Italy,Netherlands,New Zealand,Norway,Poland,South Africa,Spain,Sweden,United States
