Phase 3 Completed N=5,407 Randomized Double-blind Prevention

Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)

Deep Vein Thrombosis · Chronic Obstructive Pulmonary Disease

Source: ClinicalTrials.gov NCT00423319 ↗

Enrolled (actual)

5,407

Serious AEs

6.7%

Results posted

May 2014

Primary outcomePrimary: Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period — 1.39; 3.86 Percentage of events/patients evaluated — p=<0.0001

Summary

The purpose of this study is to learn whether apixaban can prevent the blood clots in the leg (deep vein thrombosis) and lung (pulmonary embolism) that sometimes occur after hip replacement surgery and to learn how apixaban compares with enoxaparin in preventing these clots. The safety of apixaban will also be studied

Outcome Measures

Outcome	Result	p-value
PRIMARY Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period	1.39; 3.86	<0.0001 sig
SECONDARY Rate of Composite of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During Intended Treatment Period	0.45; 1.14	<0.0001 sig
SECONDARY Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period	0.11; 0.04; 0.04; 0.00; 0.11; 0.19	—
SECONDARY Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period	0.82; 0.68; 4.08; 4.51; 4.83; 5.04	0.54
SECONDARY Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome	18; 18; 15; 21; 2; 0	—
SECONDARY Number of Participants With a Bleeding-related Adverse Event During the Treatment Period	20; 23; 19; 14; 14; 10	—
SECONDARY Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)	16; 13; 6; 5; 4; 10	—
SECONDARY Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)	20; 15; 5; 9; 2; 2	—
SECONDARY Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period	32; 19; 29; 35; 7; 5	—
SECONDARY Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period	2189; 2218; 1274; 1350; 6; 9	—
SECONDARY Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)	0; 1; 747; 752; 3; 1	—
SECONDARY Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)	0; 1; 747; 752; 3; 1	—
SECONDARY Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period	48; 67; 40; 61; 27; 54	—
SECONDARY Rates of Adjudicated Myocardial Infarction (MI)/Stroke, MI, Stroke, and Thrombocytopenia During the Intended Treatment Period	0.22; 0.26; 0.19; 0.11; 0.04; 0.15	—

Eligibility Criteria

Key Inclusion Criteria

Patients undergoing elective unilateral total hip replacement or a revision of at least 1 component of a total hip replacement.
Patients who were willing and able to undergo bilateral ascending contrast venography
Either sex, any race, 18 years and older

Key Exclusion Criteria

Known or suspected bleeding or coagulation disorder in the patient or his or her first-degree relative
Known or suspected history of heparin-induced thrombocytopenia
Known coagulopathy
Active bleeding or at high risk for bleeding
Brain, spinal, ophthalmologic, or major surgery or trauma within the past 90 days
Active hepatobiliary disease
Alcohol and/or substance abuse within the past year
Any condition for which surgery or administration of an anticoagulant is contraindicated
Two consecutive blood pressure readings within 15 to 30 minutes with supine systolic blood pressure >180 mm Hg or supine diastolic blood pressure >105 mm Hg
Clinically significant laboratory abnormalities at the enrollment visit:
Hemoglobin 2*upper limit of normal or a total bilirubin ≥ 1.5*1 (unless an alternative causative factor such as Gilbert's syndrome was identified)
Need for ongoing treatment with a parenteral or oral anticoagulant (eg, subjects with mechanical valves, warfarin eligible atrial fibrillation)
Current use of dextrans or fibrinolytics
Treatment with medications affecting coagulation or platelet function

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Data sourced from ClinicalTrials.gov (NCT00423319). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.