Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery
- Conditions
- Pulmonary EmbolismDeep Vein Thrombosis
- Interventions
- Registration Number
- NCT00452530
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3221
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Enoxaparin, 40 mg QD + Placebo Apixaban-matching placebo 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. Apixaban, 2.5 mg BID + Placebo Enoxaparin-matching placebo 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. Apixaban, 2.5 mg BID + Placebo Apixaban 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. Enoxaparin, 40 mg QD + Placebo Enoxaparin 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.
- Primary Outcome Measures
Name Time Method Rate of Adjudicated Venous Thromboembolic Event-related and All-cause Deaths With Onset During the Intended-treatment Period Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study drug Event rate=Number of events divided by the number of patients evaluated. Intended treatment period starts on the day of randomization, and for those who received study drug, ends at the later of 2 days after last dose or 14 days after the first dose of study drug; for randomized patients who did not receive study drug, the period ends 14 days after randomization.Venous thromboembolic event (VTE)=nonfatal pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or asymptomatic proximal DVT detected by ultrasound. VTE-related death=fatal PE or sudden death for which VTE could not be excluded as a cause.
- Secondary Outcome Measures
Name Time Method Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome Days 1 through 12 + 2 days (nonserious AEs, bleeding AES) or 30 days (SAES, deaths) after last dose of study drug AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Bleeding AEs=all serious or nonserious bleeding-related AEs.
Rate of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During the Intended Treatment Period Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study Event rate=Number of events divided by the number of patients evaluated. Intended treatment period starts on the day of randomization, and for those who received study drug, ends at the later of 2 days after last dose or 14 days after the first dose of study drug; for randomized patients who did not receive study drug, the period ends 14 days after randomization; for randomized patients who did not receive study drug, the period ends 14 days after randomization. Venous thromboembolic event (VTE)=nonfatal pulmonary embolism (PE), symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death=fatal PE or sudden death for which VTE could not be excluded as a cause.
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM Days 1 to 12 Event rate=Number of events divided by number of patients evaluated. Adjusted difference of event rates takes into consideration type of surgery as a stratification factor. Bleeding Criteria: Major bleeding=an event consisting of clinically overt bleeding accompanied by a decrease in hemoglobin of 2 g/dL or more and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal. CRNM bleeding= clinically overt bleeding; that satisfies none of the additional criteria required for the event to be adjudicated as a major bleeding event; that led to either hospital admission for bleeding, physician-guided medical or surgical treatment for bleeding; or a change in antithrombic treatment.
Trial Locations
- Locations (1)
Local Institution
🇬🇧Epsom, Surrey, United Kingdom