What's New
Investigational anticoagulant targeting factor XIa (January 2020)
Osocimab is an investigational monoclonal antibody directed against factor XIa, a new target for anticoagulant development. In a randomized trial comparing osocimab with enoxaprin or apixaban in over 800 individuals undergoing elective knee arthroplasty, osocimab, 1.8 mg/kg preoperatively, had similar rates of postoperative venous thromboembolism (VTE) and bleeding as apixaban and lower rates of VTE and bleeding than enoxaparin. The half-life of osocimab is 30 to 44 days, allowing single-dose administration for surgical prophylaxis.
Effect of Osocimab in Preventing Venous Thromboembolism Among Patients Undergoing Knee Arthroplasty: The FOXTROT Randomized Clinical Trial.
Weitz JI, Bauersachs R, Becker B, Berkowitz SD, Freitas MCS, Lassen MR, Metzig C, Raskob GE
JAMA. 2020;323(2):130.
Importance :
The efficacy of factor XIa inhibition for thromboprophylaxis is unknown. Osocimab is a long-acting, fully human monoclonal antibody that inhibits factor XIa.
Objective :
To compare different doses of osocimab with enoxaparin and apixaban for thromboprophylaxis in patients who have undergone knee arthroplasty.
Design, Setting, and Participants :
Randomized, open-label, adjudicator-blinded, phase 2 noninferiority trial with observer blinding for osocimab doses, conducted at 54 hospitals in 13 countries. Adult patients undergoing unilateral knee arthroplasty were randomized from October 2017 through August 2018 and followed up until January 2019.
Interventions :
Single intravenous osocimab postoperative doses of 0.3 mg/kg (n = 107), 0.6 mg/kg (n = 65), 1.2 mg/kg (n = 108), or 1.8 mg/kg (n = 106); preoperative doses of 0.3 mg/kg (n = 109) or 1.8 mg/kg (n = 108); or 40 mg of subcutaneous enoxaparin once daily (n = 105) or 2.5 mg of oral apixaban twice daily (n = 105) for at least 10 days or until venography.
Main Outcomes and Measures :
The primary outcome was venous thromboembolism incidence between 10 and 13 days postoperatively (assessed by mandatory bilateral venography performed 10 to 13 days after surgery or confirmed symptomatic deep vein thrombosis or pulmonary embolism). A 5% noninferiority margin compared with enoxaparin was chosen. The primary safety outcome of major or clinically relevant nonmajor bleeding was assessed until 10 to 13 days postoperatively.
Results :
Of 813 randomized participants (mean [SD]age, 66.5 years [8.2 years]; body mass index, 32.7 [5.7]; and 74.2% women), 600 were included in the per-protocol population used for the primary analysis. The primary outcome occurred in 18 patients (23.7%) receiving 0.3 mg/kg, 8 (15.7%) receiving 0.6 mg/kg, 13 (16.5%) receiving 1.2 mg/kg, and 14 (17.9%) receiving 1.8 mg/kg of osocimab postoperatively; 23 (29.9%) receiving 0.3 mg/kg and 9 (11.3%) receiving 1.8 mg/kg of osocimab preoperatively; 20 (26.3%) receiving enoxaparin; and 12 (14.5%) receiving apixaban. Osocimab given postoperatively met criteria for noninferiority compared with enoxaparin with risk differences (1-sided 95% CIs) of 10.6% (95% CI, -1.2% to∞) at the 0.6-mg/kg dose; 9.9% (95% CI, -0.9% to∞) at the 1.2-mg/kg dose, and 8.4% (95% CI, -2.6 to∞) at the 1.8-mg/kg dose. The preoperative dose of 1.8 mg/kg of osocimab met criteria for superiority compared with enoxaparin with a risk difference of 15.1%; 2-sided 90% CI, 4.9% to 25.2%). Postoperative and preoperative doses of 0.3 mg/kg of osocimab did not meet the prespecified criteria for noninferiority, with risk differences (1-sided 95% CIs) of 2.6% (95% CI, -8.9% to∞) and -3.6% (95% CI, -15.5% to∞), respectively. Major or clinically relevant nonmajor bleeding was observed in up to 4.7% of those receiving osocimab, 5.9% receiving enoxaparin, and 2% receiving apixaban.
Conclusions and Relevance :
Among patients undergoing knee arthroplasty, postoperative osocimab 0.6 mg/kg, 1.2 mg/kg, and 1.8 mg/kg met criteria for noninferiority compared with enoxaparin, and the preoperative 1.8-mg/kg dose of osocimab met criteria for superiority compared with enoxaparin for the primary outcome of incidence of venous thromboembolism at 10 to 13 days postoperatively. Further studies are needed to establish efficacy and safety of osocimab relative to standard thromboprophylaxis.
Trial RegistrationClinicalTrials.gov Identifier: NCT03276143.
REF. UpToDate 2020.03.05
