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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 3

Conditions: Pulmonary Embolism; Deep Vein Thrombosis

Treatments: Drug: Enoxaparin-matching placebo; Drug: Apixaban-matching placebo; Drug: Apixaban; Drug: Enoxaparin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00423319

CV185-035

Details and patient eligibility

About

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

Enrollment: 5,407 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 <10 g/dL
• Platelet count <100,000/mm^3
• Creatinine clearance <30 mL/min, as estimated by the method of Cockcroft and Gault
• Alanine aminotransferase or aspartate aminotransferase >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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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5,407 participants in 2 patient groups

Apixaban, 2.5 mg BID plus placebo

Active Comparator group

Description:

Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)

Treatment:

Drug: Enoxaparin-matching placebo

Drug: Apixaban

Enoxaparin, 40 mg QD plus placebo

Experimental group

Description:

Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID

Treatment:

Drug: Enoxaparin

Drug: Apixaban-matching placebo