zation included heart failure, respiratory failure, infectious disease, rheumatic disease, or ischemic stroke. At study initiation eligible patients were required to have one of the following additional risk factors for VTE:
≥ 75 years of age,
60 through 74 years of age with D-dimer ≥ 2 ULN, or
40 through 59 years of age with D-dimer ≥ 2 ULN and a history of either VTE or cancer.
A total of 7,513 patients were randomized 1:1 to:
BEVYXXA arm (BEVYXXA 160 mg orally on Day 1, then 80 mg once daily for 35 to 42 days AND enoxaparin subcutaneous placebo once daily for 6 to 14 days),
OR
Enoxaparin arm (enoxaparin 40 mg subcutaneously once daily for 6 to 14 days AND BEVYXXA placebo orally once daily for 35 to 42 days).
Patients with severe renal impairment (creatinine clearance ≥ 15 and < 30 mL/min) received reduced doses of study medications (BEVYXXA 80 mg loading dose, then 40 mg once daily or enoxaparin 20 mg once daily) along with corresponding placebo.
Patients taking a concomitant P-gp inhibitor received BEVYXXA 80 mg loading dose, then 40 mg once daily or enoxaparin 40 mg subcutaneously once daily for 6 to 14 days along with corresponding placebo.
Baseline characteristics were balanced between the treatment groups. The population was 55% female, 93% White, 2% Black, 0.2% Asian, and 5% others. The most preva lent acute medical illness at hospitalization was acutely decompensated heart failure (45%), followed by acute infection without septic shock (29%), acute respiratory failure (12%), acute ischemic stroke (11%) and acute rheumatic disorders (3%). The mean and median ages were 76.4 and 77 years, respectively, with 68% of patients ≥ 75 years of age, 97% were severely immobilized at study entry, and 62% had D-dimer ≥ 2 × ULN.
While the APEX Study was ongoing (after 35% enrollment), the study was amended to restrict further enrollment to patients ≥ 75 years of age or with D-dimer values ≥ 2 × ULN. The APEX trial excluded patients whose condition required prolonged anticoagulation (e.g., concurrent VTE, atrial fibrillation, cardiac valve prosthesis), were at increased risk of bleeding, had liver dysfunction, were on dual antiplatelet therapy, or patients who had both severe renal insufficiency (CrCl 15-29 ml/min) and required the concomitant use of a P-gp inhibitor.
The efficacy of BEVYXXA was based upon the composite outcome of the occurrence of any of the following events up to Day 35 visit:
Asymptomatic proximal Deep Vein Thrombosis (DVT) (detected by ultrasound),
Symptomatic proximal or distal DVT,
Non-fatal Pulmonary Embolism (PE), or
VTE-related death.
Efficacy analyses were performed based on the modified Intent-to-Treat (mITT) population. The mITT population consisted of all patients who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy outcome components. A total of 7,441 patients (N=3,721 for BEVYXXA and N=3,720 for enoxaparin) were included in the mITT population.
The efficacy results for the APEX trial are provided in Table 5 below.
Table 5: Efficacy Outcomes in APEX Trial (mITT Population)
BEVYXXA
N=3,721
n (%)* Enoxaparin
N=3,720
n (%) * Relative Risk
(95% CI) †
* Percentages and event rates are based on the total number of patients and events included in each treatment group. † Relative Risk (BEVYXXA arm versus enoxaparin arm) is based on the Mantel-Haenszel test stratified by the dosing strata and |
