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

Bristol-Myers Squibb3,221 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

3,221

Conditions

Deep Vein Thrombosis Pulmonary Embolism

Interventions

EnoxaparinDRUG

40 mg, administered once daily by subcutaneous injection, for 12 days

ApixabanDRUG

2.5 mg, administered twice daily as tablets, for 12 days

Enoxaparin-matching placeboDRUG

Administered once daily by subcutaneous injection

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (122)

Outcomes

Primary Outcomes

Rate of Adjudicated Venous Thromboembolic Event-related and All-cause Deaths With Onset During the Intended-treatment Period

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.

Time frame: 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

Secondary Outcomes

Rate of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During the Intended Treatment Period

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.

Time frame: 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

Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM

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.

Data from ClinicalTrials.gov

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