A Phase 3 Randomized, Double-Blind Active-Controlled (Enoxaparin), Parallel-Group, Multi-Center Study to Evaluate the Safety and Efficacy of Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement Surgery

NCT00371683 Phase 3 COMPLETED Results posted

The purpose of this study is to learn if apixaban can prevent blood clots in the leg (deep vein Thrombosis \[DVT\]) and lung (pulmonary embolism \[PE\]) that sometimes occur after knee replacement surgery and to learn how apixaban compares to enoxaparin (Lovenox®) for preventing these clots. The safety of apixaban will also be studied.

Details

Lead sponsor	Bristol-Myers Squibb
Phase	Phase 3
Status	COMPLETED
Enrolment	3608
Start date	2006-11
Completion	2008-05

Conditions

• Deep Vein Thrombosis
• Pulmonary Embolism

Interventions

• Enoxaparin + Placebo
• Apixaban + Placebo

Primary outcomes

• Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects — From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
  An Independent Central Adjudication Committee (ICAC) adjudicated all venograms, suspected symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed and reported as percentage (%). Surgery=Day 1; Randomization/Treatment started on Day of Surgery or the next day (Day 1 or Day 2). A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. Intended Treatment Period=starts on the day of randomization; for treated participants, the period ends at the latter of 2 days after last dose of study drug or 14 days after the first dose of study drug; for randomized participants who were not treated, the period ends 14 days after randomization.
• Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population — First dose of study drug to last dose, plus 2 days post last dose
  ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Clinically relevant (CR); Non-Major (N-M) Bleeding. Day 1=Day of surgery. Treatment started (first dose) day of surgery or next day. Treatment continued for 12 days.
• Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period — Last dose of study drug to Day 72 (60 days)
  ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Follow up Period was from the end of the treatment period (last dose) up to 60 days post last dose, Day 72.

Countries

United States, Argentina, Australia, Brazil, Canada, Denmark, Hungary, Israel, Mexico, Poland, Russia, Sweden, Turkey (Türkiye)