The purpose of this study is to assess if 10 mg BAY 59-7939, taken once daily as a tablet, is safe and can help prevent blood clots forming after a hip replacement operation.
Venous thromboembolism (VTE) is a common, potentially fatal complication of major orthopaedic surgery. Pharmacologic thromboprophylaxis is recommended for patients undergoing total hip arthroplasty (THA) for a minimum of 10 days, and up to 35 days. However, extended thromboprophylaxis is not universally used. Therefore, this trial was conducted to evaluate the potential benefits of extended thromboprophylaxis after THA. RECORD2 is the largest, prospective, randomized clinical trial conducted to date, in this indication. This global, phase III, double-blind trial, was designed to compare short-term thromboprophylaxis with a low molecular weight heparin - enoxaparin - with extended thromboprophylaxis for up to 5 weeks with a novel, oral, direct Factor Xa inhibitor - rivaroxaban after THA. Patients received subcutaneous enoxaparin 40 mg once daily (od), beginning the evening before surgery, continuing for 10–14 days (short-term prophylaxis), and followed by placebo until day 35±4, or oral rivaroxaban 10 mg od beginning 6–8 hours after surgery and continuing for 35±4 days (extended prophylaxis). Mandatory, bilateral venography was conducted at the end of the extended treatment period. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The main secondary efficacy endpoint was major VTE; the composite of proximal DVT, non-fatal PE, and VTE-related death. Major and non-major bleeding during double-blind treatment were the primary and secondary safety endpoints, respectively. A total of 2509 patients were randomized; 2457 were included in the safety population and 1733 in the modified intention-to-treat (mITT) population. Extended thromboprophylaxis with rivaroxaban was associated with a significant reduction in the incidence of the primary efficacy endpoint and major VTE, compared with short-term thromboprophylaxis with enoxaparin (Table). The incidences of major and non-major bleeding were similar in both groups (Table). In conclusion, extended duration rivaroxaban was significantly more effective than short term enoxaparin for the prevention of VTE, including major VTE, in patients undergoing THA. Furthermore, this large trial demonstrated that extended thromboprophylaxis provides substantial benefits for patients undergoing THA, and that the oral, direct Factor Xa inhibitor rivaroxaban provides a safe and effective option for such a strategy.
CONTEXTE: Le risque de thromboembolie veineuse est élevée après une arthroplastie totale de hanche et pourraient persister après la sortie de l'hôpital. Notre but était de comparer l'utilisation du rivaroxaban pour la thromboprophylaxie prolongée à court terme une thromboprophylaxie par énoxaparine. MÉTHODES: 2509 patients devant subir une arthroplastie totale de hanche élective ont été randomisés, stratifié selon le centre, avec un code généré par ordinateur randomisation, de recevoir par voie orale de rivaroxaban 10 mg une fois par jour pendant 31-39 jours (avec injection de placebo pendant 10-14 jours n = 1252), ou 40 mg d'énoxaparine sous-cutanée une fois par jour pour 10-14 jours (avec comprimé placebo pour 31-39 jours; n = 1257). Le critère principal d'efficacité était un critère composite de thrombose veineuse profonde (symptomatiques ou asymptomatiques détectées par obligatoire, phlébographie bilatérale), non-embolie pulmonaire fatale, et la mortalité toutes causes jusqu'au jour 30-42. Analyses ont été effectuées dans le modifiés intention de traiter la population, qui se composait de tous les patients qui avaient reçu au moins une dose de médicament à l'étude, avait subi une intervention chirurgicale prévue, et a eu une évaluation adéquate de la maladie thromboembolique. Cette étude est inscrite au ClinicalTrials.gov, numéro NCT00332020. RÉSULTATS: L'intention de traiter modifiée de la population pour l'analyse des résultats d'efficacité primaire se composait de 864 patients dans le groupe rivaroxaban et 869 dans le groupe énoxaparine. Le résultat principal a été observé dans 17 cas (2,0%) patients dans le groupe rivaroxaban, comparativement à 81 (9,3%) dans le groupe énoxaparine (réduction du risque absolu de 7,3%, IC à 95% 05.02 à 09.04, p <0,0001). L'incidence des saignements en cours de traitement est sensiblement la même dans les deux groupes (81 [6,6%] des événements en 1228 patients dans le rivaroxaban la population la sécurité vs 68 [5,5%] de 1229 patients dans la population la sécurité énoxaparine; p = 0,25). INTERPRETATION: thromboprophylaxie par rivaroxaban étendue était significativement plus efficace que l'énoxaparine à court terme plus un placebo pour la prévention de la thromboembolie veineuse, y compris les événements symptomatiques, chez les patients subissant une arthroplastie totale de hanche.
Four phase III studies compared oral rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism (VTE) after total hip or knee arthroplasty (THA or TKA). A pooled analysis of these studies compared the effect of rivaroxaban with enoxaparin on symptomatic VTE plus all-cause mortality and bleeding events, and determined whether these effects were consistent in patient subgroups. Patients (N=12,729) aged ≥18 years and scheduled for elective THA or TKA received rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily or 30 mg every 12 hours. The composite of symptomatic VTE and all-cause mortality, the prespecified primary efficacy endpoint and adjudicated bleeding events were analysed in the day 12± 2 active treatment pool. Subgroup analyses of these outcomes were performed over the total treatment period. In the day 12± 2 pool, the primary efficacy endpoint occurred in 29/6,183 patients receiving rivaroxaban (0.5%) versus 60/6,200 patients receiving enoxaparin (1.0%; p=0.001). Major bleeding occurred in 21 (0.3%) versus 13(0.2%) patients, p=0.23; major plus non-major clinically relevant bleeding in 176(2.8%) versus 152 (2.5%) patients, p=0.19; and any bleeding in 409 (6.6%) versus 384 (6.2%) patients, p=0.38, respectively. The reduction of symptomatic VTE plus all-cause mortality was consistent across prespecified subgroups (age, gender, body weight, creatinine clearance) in the total treatment period. Compared with enoxaparin regimens, rivaroxaban reduces the composite of symptomatic VTE and all-cause mortality after elective THA or TKA, with a small increase in bleeding, no signs of compromised liver safety and fewer serious adverse events.
The purpose of this study is to assess if 10 mg BAY 59-7939, taken once daily as a tablet, is safe and can help prevent blood clots forming after a hip replacement operation.
Devis de recherche»Essai contrôlé randomisé (ECR)
Pays»Australia,Brazil,Canada,China,Colombia,Denmark,Estonia,India,Indonesia,Italy,Korea, Republic of,Latvia,Lithuania,Mexico,New Zealand,Norway,Peru,Portugal,South Africa,Sweden,United Kingdom,United States
