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 within patients hospitalized for acute medical illness, and to learn how apixaban compares to enoxaparin (Lovenox®) for preventing these clots. The safety of apixaban will also be studied.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
6,758
Apixaban: Twice daily, 30 days Placebo: Once daily, 6-14 days
Enoxaparin: Once daily, 6-14 days Placebo: Twice daily, 30 days
Incidence of Composite of Adjudicated Total Venous Thromboembolism (VTE) and VTE-related Death During the Intended Treatment Period - Primary Efficacy Population
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. Intended Treatment Period=period that started on day of randomization: period ended (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; period ended (for not treated) 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. All efficacy events were adjudicated by the Independent Central Adjudication Committee (ICAC). Event rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Major Bleeding During the Treatment Period in Treated Participants
Major bleeding was adjudicated by an ICAC using criteria from the International Society on Thrombosis and Hemostasis (ISTH) and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or bleeding in a critical site or bleeding which is fatal. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Day 1, first dose of study drug, to last dose of study drug plus 2 days
Incidence of Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants
Bleeding was adjudicated by an ICAC using criteria from the ISTH. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis, if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
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University Of Alabama At Birmingham Hospital
Birmingham, Alabama, United States
Heart Center Research, Llc
Huntsville, Alabama, United States
Arizona Pulmonary Specialists, Ltd.
Phoenix, Arizona, United States
Az Pulmonary Specialists Ltd
Scottsdale, Arizona, United States
Fort Smith Lung Center
Fort Smith, Arkansas, United States
Scripps Clinic/Scripps Health And Green Hospital
La Jolla, California, United States
Va Long Beach Healthcare System
Long Beach, California, United States
Univ. Of Southern Calif. /Norris Comprehensive Cancer Center
Los Angeles, California, United States
Dr. Felt Medical Office
Oakland, California, United States
Stanford University
Stanford, California, United States
...and 286 more locations
Time frame: Day 1, first dose of study drug, to last dose of study drug plus 2 days
Incidence of Composite of Major or Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants
Bleeding was adjudicated by an ICAC using criteria from the ISTH. Major bleeding: acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or bleeding in a critical site or bleeding which is fatal. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage; rectal blood loss. Treatment Period=onset from first dose of study drug through 2 days after last dose of study drugs. Incidence: Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Day 1, first dose of study drug, to last dose of study drug plus 2 days
Incidence of All Bleeding During the Treatment Period in Treated Participants
Bleeding was adjudicated by an ICAC using criteria from the ISTH. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs, for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Day 1, first dose of drug to last dose of drug plus 2 days
Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Key Secondary Efficacy Evaluable Participants
Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Key Secondary Efficacy population: all who received at least 1 dose of parenteral study drug and: (those without suspected VTE events during Parenteral Treatment) had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or (those with suspected VTE events during Parenteral Treatment) had those suspected VTE events adjudicated as non-events, and had an adjudicated evaluable ultrasound performed at the end of Parenteral Treatment; or had an adjudicated total VTE during Parenteral Treatment; or had an adjudicated VTE-related death during Parenteral Treatment. Event rate (%): n/N\*100 (n=number with observation; N=total secondary efficacy evaluable participants).
Time frame: Day 1 to last dose of parenteral study drug plus 1 day
Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Secondary Efficacy Evaluable Participants
Parenteral study drug=active or placebo enoxaparin. Parenteral treatment: started on the first dose of parenteral study drug and ended the day after the last dose of parenteral study drug. Secondary Efficacy Evaluable includes those who had an adjudicated, evaluable ultrasound at end of parenteral treatment and for those with a suspected symptomatic event, the result of the adjudication for the symptomatic event was not inadequate; or those with an adjudicated event that was part of the composite endpoint.. Event rate (%): n/N\*100 (n=number with observation; N=total secondary efficacy evaluable participants).
Time frame: Day 1 to last dose of parenteral study drug plus 1 day
Incidence of Adjudicated Total VTE or All-Cause Death With Onset During the Intended Treatment Period
Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal (N-F) PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. All-Cause Death (A-C Death). Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated Proximal DVT, Non-Fatal PE or All-Cause Death With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death, With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated VTE-Related Death With Onset During the Intended Treatment Period in Randomized Participants
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated Symptomatic VTE or All-Cause Death With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Symptomatic Adjudicated VTE or VTE-Related Death With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of All VTE or Major Bleeding or All-Cause Death During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. VTE: nonfatal PE, symptomatic DVT, or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE cannot be excluded as a cause. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated PE With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. PE: non-fatal or fatal. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated Non-Fatal PE With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated Symptomatic DVT With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated Proximal DVT With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated Symptomatic Distal DVT With Onset During the Intended Treatment Period
Events were adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated Symptomatic Proximal DVT With Onset During the Intended Treatment Period
Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Incidence of Adjudicated Asymptomatic Proximal DVT With Onset During the Intended Treatment Period
A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. Events adjudicated by ICAC. Intended Treatment Period=period that starts on day of randomization: period ends (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; (for not treated) period ends 32 days after randomization. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Time frame: Intended Treatment Period
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants
Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for AEs, and 30 days after last dose of study drugs for SAEs and deaths.
Time frame: Day 1, first dose of study drug, to last dose of study drug plus 2 days (AEs), plus 30 days (SAEs, Deaths)
Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period
Diastolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken with the participant either sitting, standing, or supine.
Time frame: Day 1 to last dose of study drug plus 2 days
Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period
Systolic blood pressure was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Blood pressure was measured in millimeters of mercury (mmHg) and could have been taken either sitting, standing, or supine.
Time frame: Day 1 to last dose of study drug plus 2 days
Mean Change From Baseline in Heart Rate in Treated Participants
Heart Rate was obtained during Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days. Heart rate was measured in beats per minute (bpm) and could have been taken with participants either sitting, standing, or supine.
Time frame: Day 1 to last dose of study drug plus 2 days
Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants
Lower limit of normal (LLN). Upper limit of normal (ULN). Pre-therapy (PreRx). Absolute (Abs) neutrophil count, bands + neutrophils (ANC). Cells per microliter (c/µL). Grams per deciliter (g/dL). Cells per Liter (c/L). Millimeter (MM). Absolute (Abs). Hemoglobin: \>2 g/dL decrease compared to PreRx value or value \<=8 g/dL; Hematocrit: \<0.75\*PreRx; Erythrocytes: \<0.75\*PreRx c/µL; Leukocytes: \<0.75\*LLN or \> 1.25\*ULN, if PreRx \<LLN then use \<0.8\*PreRx or \>ULN, if PreRx \>ULN then use \>1.2\*PreRx or \< LLN; Platelet count: \< 100\*10\^9 c/L; ANC: \< 1.00\*10\^3 c/µL; Abs eosinophils: \> 0.75\*10\^3 c/µL; Abs Basophils: \> 400/MM\^3; Abs Monocytes \> 2000/MM\^3; Abs Lymphocytes: \< 0.750\*10\*3 c/ µL or \> 7.5\*10\^3 c/ µL. Samples were obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.
Time frame: Day 1 to last dose of study drug plus 2 days
Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants
Bicarbonate milliequivalents/Liter (mEq/L) Low/High: \< 0.75\*LLN or \> 1.25\*ULN, or if PreRx \< LLN then use \< 0.75\* PreRx or \> ULN if PreRx \> ULN then use \> 1.25\*PreRx or \< LLN; Serum Calcium mg/dL Low/High: \< 0.8\*LLN or \> 1.2\*ULN, or if PreRx \< LLN then use \< 0.75\*PreRx or \> ULN if PreRx \> ULN then use \> 1.25\*PreRx or \< LLN; Serum Chloride mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use \< 0.9\*PreRx or \> ULN if PreRx \> ULN then use \> 1.1\*PreRx or \< LLN; Serum Potassium mEq/L: \< 0.9\*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use \< 0.9\*PreRx or \> ULN if PreRx \> ULN then use \> 1.1\*PreRx or \< LLN; Serum Sodium mEq/L: \< 0.95\*LLN or \> 1.05\*ULN, or if PreRx \< LLN then use \< 0.95\*PreRx or \> ULN if PreRx \> ULN then use \> 1.05\*PreRx or \< LLN. Samples obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.
Time frame: Day 1 to last dose of study drug plus 2 days
Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants
Blood urea nitrogen (BUN), milligrams/deciliter (mg/dL), units per liter (U/L). BUN mg/dL \> 1.5\*ULN; Creatinine mg/dL: \> 1.5\*ULN; Alanine aminotransferase (ALT) U/L: \> 3\*ULN; Aspartate aminotransferase (AST) U/L: \> 3\*ULN; Alkaline phosphatase U/L: \> 2\*ULN; Bilirubin Direct mg/dL: \> 1.5\*ULN; Bilirubin Total mg/dL: \> 2\*ULN. Samples for laboratories obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) plus 2 days.
Time frame: Day 1 to last dose of study drug plus 2 days
Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants
Creatine kinase High: \>5\*ULN Units/Liter (U/L); Total Protein High/Low: \< 0.9 \*LLN or \> 1.1\*ULN, or if PreRx \< LLN then use 0.9\* PreRx or \> ULN if PreRx \> ULN then use 1.1 \*PreRx or \<LLN; Uric acid High: \> 1.5\* ULN, or if PreRx \> ULN then use \> 2 \*PreRx. Glucose Fasting: \<0.9\*LLN or \> 1.5\*ULN or if PreRx \< LLN then use \< 0.8\*PreRx or \> ULN, if PreRx \> ULN then use \>2.0\*PreRx. Samples obtained at Screening/Enrollment Visit (Day 1, prior to drug being administered), on the day of hospital discharge, Day 30 (last day of treatment) ± 2days.
Time frame: Day 1 to last dose of study drug plus 2 days
Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants
Events of Special Interest include: adjudicated thrombocytopenia, adjudicated myocardial infarction (MI), adjudicated stroke, and adjudicated MI or stroke. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants). Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs.
Time frame: Day 1 to last dose of study drug plus 2 days
Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements
Special interest include: liver function test increases, AEs related to liver function, and neurologic AEs. Treatment Period includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drug when summarizing AEs and through 30 days after the last dose when summarizing SAEs.
Time frame: Day 1 to last dose of study drug plus 2 days (AEs) and plus 30 days (SAEs)
Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants
Liver function tests: Alanine aminotransferase (ALT) U/L; Aspartate aminotransferase (AST) U/L; Alkaline phosphatase U/L; Total Bilirubin (TBili) mg/dL. Elevations consist of \>3\*Upper Limit of Normal (ULN) for ALT and AST and elevation of \>2\*ULN for Bilirubin.
Time frame: Day 1 to last dose of study drug plus 2 days