Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery (ADVANCE-2)

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 3

Conditions: Pulmonary Embolism; Deep Vein Thrombosis

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00452530

EUdraCT: 2006-006896-19

CV185-047

Details and patient eligibility

About

The purpose of this study is to learn whether apixaban prevents the development of blood clots in the leg (deep vein thrombosis) and lung (pulmonary embolism), which sometimes occur after knee replacement surgery, and to compare the efficacy of apixaban with that of enoxaparin (Lovenox®) in the prevention of these clots. The safety of apixaban will also be studied.

Enrollment: 3,221 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria

• Patients scheduled for either elective unilateral or same-day bilateral total knee replacement surgery (TKR) or a revision of at least 1 component of a TKR
• Patients willing and able to undergo bilateral ascending contrast venography

Key Exclusion Criteria

• Known or suspected hereditary or acquired bleeding or coagulation disorders in the participant 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, in the opinion of the investigator, surgery or administration of an anticoagulant was 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 level >2*upper limit of normal (ULN) or a total bilirubin ≥1.5*ULN (unless an alternative causative factor such as Gilbert's syndrome was identified)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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3,221 participants in 2 patient groups

Apixaban, 2.5 mg BID + Placebo

Experimental group

Description:

Participants received apixaban, 2.5-mg tablets twice daily (BID), plus a matching enoxaparin-placebo injection 12 (±3) hours prior to hip-replacement surgery through 11 (±2) days after the day of surgery.

Treatment:

Drug: Enoxaparin-matching placebo

Drug: Apixaban

Enoxaparin, 40 mg QD + Placebo

Active Comparator group

Description:

Participants received enoxaparin, 40-mg subcutaneous injection once daily (QD), plus a matching apixaban-placebo tablet 12 (±3) hours prior to hip-replacement surgery through 11 (±2) days after the day of surgery.

Treatment:

Drug: Enoxaparin

Drug: Apixaban-matching placebo