Trial Outcomes & Findings for Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery (NCT NCT00452530)
NCT ID: NCT00452530
Last Updated: 2014-07-09
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
3221 participants
Primary outcome timeframe
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
Results posted on
2014-07-09
Participant Flow
Of 3221 patients enrolled, 3057 were randomized. Primary participants=those who were randomized and had an adjudicated evaluable bilateral venogram or an adjudicated venous thromboembolic event or died. Evaluable participants=those with significant protocol deviations expected to affect the primary endpoint.
Participant milestones
| Measure |
Apixaban, 2.5 mg BID + Placebo
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Overall Study
STARTED
|
1528
|
1529
|
|
Overall Study
Received Treatment
|
1501
|
1508
|
|
Overall Study
Evaluable Participants
|
907
|
921
|
|
Overall Study
Primary Participants
|
976
|
997
|
|
Overall Study
COMPLETED
|
1392
|
1393
|
|
Overall Study
NOT COMPLETED
|
136
|
136
|
Reasons for withdrawal
| Measure |
Apixaban, 2.5 mg BID + Placebo
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Adverse Event
|
40
|
44
|
|
Overall Study
Withdrawal by Subject
|
68
|
57
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Poor compliance/noncompliance
|
1
|
2
|
|
Overall Study
No longer met study criteria
|
18
|
22
|
|
Overall Study
Other
|
7
|
11
|
Baseline Characteristics
Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery
Baseline characteristics by cohort
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=1528 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=1529 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
Total
n=3057 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67 Years
STANDARD_DEVIATION 9.85 • n=5 Participants
|
67 Years
STANDARD_DEVIATION 9.82 • n=7 Participants
|
67 Years
STANDARD_DEVIATION 9.84 • n=5 Participants
|
|
Age, Customized
Younger than 65 years
|
632 Participants
n=5 Participants
|
636 Participants
n=7 Participants
|
1268 Participants
n=5 Participants
|
|
Age, Customized
65 years to younger than 75 years
|
608 Participants
n=5 Participants
|
576 Participants
n=7 Participants
|
1184 Participants
n=5 Participants
|
|
Age, Customized
75 years and older
|
288 Participants
n=5 Participants
|
317 Participants
n=7 Participants
|
605 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1089 Participants
n=5 Participants
|
1127 Participants
n=7 Participants
|
2216 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
439 Participants
n=5 Participants
|
402 Participants
n=7 Participants
|
841 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
1216 Participants
n=5 Participants
|
1211 Participants
n=7 Participants
|
2427 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
14 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
252 Participants
n=5 Participants
|
254 Participants
n=7 Participants
|
506 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian/Other Pacific Islander
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other [Not specified]
|
45 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
91 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic/Latino
|
53 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
110 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity not reported
|
1475 Participants
n=5 Participants
|
1471 Participants
n=7 Participants
|
2946 Participants
n=5 Participants
|
|
Region of Enrollment
Philippines
|
12 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
61 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
181 Participants
n=5 Participants
|
182 Participants
n=7 Participants
|
363 Participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
150 Participants
n=5 Participants
|
156 Participants
n=7 Participants
|
306 Participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
43 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Region of Enrollment
Chile
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Colombia
|
36 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
69 Participants
n=5 Participants
|
69 Participants
n=7 Participants
|
138 Participants
n=5 Participants
|
|
Region of Enrollment
India
|
92 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
184 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
72 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
|
Region of Enrollment
Malaysia
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
26 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
56 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
112 Participants
n=5 Participants
|
|
Region of Enrollment
China
|
90 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
180 Participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
40 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
156 Participants
n=5 Participants
|
151 Participants
n=7 Participants
|
307 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
63 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
124 Participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
48 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
98 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
17 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
60 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
27 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
41 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
Norway
|
35 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
122 Participants
n=5 Participants
|
122 Participants
n=7 Participants
|
244 Participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Type of Risk Factor
Knee replacement
|
257 Participants
n=5 Participants
|
286 Participants
n=7 Participants
|
543 Participants
n=5 Participants
|
|
Type of Risk Factor
Hip replacement
|
90 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
170 Participants
n=5 Participants
|
|
Type of Risk Factor
Hip or knee fracture surgery
|
55 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
104 Participants
n=5 Participants
|
|
Type of Risk Factor
Deep vein thrombosis
|
36 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
|
Type of Risk Factor
Pulmonary embolism
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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 drugPopulation: The primary efficacy data set (all randomized participants who, during the Intended Treatment Period, had an adjudicated and evaluable bilateral venogram, an adjudicated venous thrombolytic event; or died due to any cause.)
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=976 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=997 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Rate of Adjudicated Venous Thromboembolic Event-related and All-cause Deaths With Onset During the Intended-treatment Period
|
15.06 Percentage of events/patients evaluated
Interval 12.95 to 17.46
|
24.37 Percentage of events/patients evaluated
Interval 21.81 to 27.14
|
SECONDARY outcome
Timeframe: 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 studyPopulation: Randomized participants with either an adjudicated and evaluable bilateral proximal venogram or an adjudicated event associated with the endpoint, 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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=1195 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=1199 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Rate of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During the Intended Treatment Period
|
1.09 Percentage of events/patients evaluated
Interval 0.62 to 1.88
|
2.17 Percentage of events/patients evaluated
Interval 1.47 to 3.18
|
SECONDARY outcome
Timeframe: Days 1 to 12Population: All participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=1501 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=1508 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM
CRNM (n=44, 58)
|
2.93 Percentage of events/patients evaluated
Interval 2.19 to 3.93
|
3.85 Percentage of events/patients evaluated
Interval 2.98 to 4.95
|
|
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM
Major bleeding (n=9, 14)
|
0.60 Percentage of events/patients evaluated
Interval 0.3 to 1.16
|
0.93 Percentage of events/patients evaluated
Interval 0.54 to 1.57
|
|
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM
Major bleeding or CRNM (n=53, 72)
|
3.53 Percentage of events/patients evaluated
Interval 2.71 to 4.6
|
4.77 Percentage of events/patients evaluated
Interval 3.81 to 5.98
|
|
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM
Any bleeding
|
6.93 Percentage of events/patients evaluated
Interval 5.75 to 8.34
|
8.36 Percentage of events/patients evaluated
Interval 7.06 to 9.87
|
SECONDARY outcome
Timeframe: Days 1 through 12 + 2 days (nonserious AEs, bleeding AES) or 30 days (SAES, deaths) after last dose of study drugPopulation: All participants who received at least 1 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.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=1501 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=1508 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome
SAE
|
72 Participants
|
88 Participants
|
|
Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome
Bleeding AE
|
90 Participants
|
112 Participants
|
|
Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome
Discontinuations due to AEs
|
40 Participants
|
44 Participants
|
|
Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome
Deaths
|
2 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (±5 days) of follow-upPopulation: All participants who received at least 1 dose of study drug. n=number of participants with available measurements
preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal; abs=absolute. Hemoglobin (g/dL): \>2 decrease from preRx value or value \<=8; hematocrit (%): \<0.75\*preRx; platelets: \<100\*10\^9 cells/L; erythrocytes (\*10\^6 cells/μL): \<0.75\*preRx; leukocytes: \<0.75\*LLN or \>1.25\*ULN, or if preRx \<LLN, use \<0.8\*preRx or \>ULN if preRx \>ULN use \>1.2\*preRx or \<LLN; abs basophils: \>400/mm\^3; abs eosinophils: \> 0.750\*10\^3 cells/µL; abs lymphocytes: \<0.750\*10\*3 cells/ µL or \>7.50\*10\^3 c/ µL; abs monocytes \> 2000/mm\^3; abs neutrophils: \<1.0\*10\^3 cells/μL; ALP (U/L): \>2\*ULN; ALT, AST (U/L): \>3\*ULN; U/L; bilirubin, direct (mg/dL): \>1.5\*ULN; bilirubin, total (mg/dL): \>2\*ULN; BUN (mg/dL): \>2\*ULN; creatinine (mg/dL): \>1.5\*ULN.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=1501 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=1508 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Leukocytes, high (n=1457, 1471)
|
193 Participants
|
213 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Alanine aminotransferase (ALT), high (n=1459,1472)
|
32 Participants
|
26 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Bilirubin, total (high) (n=1461,1476)
|
15 Participants
|
9 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Creatinine (high) (n=1447,1458)
|
17 Participants
|
23 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Hemoglobin, low (n=1424, 1442)
|
1127 Participants
|
1178 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Hematocrit, low n=(1369, 1396)
|
668 Participants
|
723 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Platelet count, low (n=1413, 1425)
|
7 Participants
|
5 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Erythrocytes, low (n=1368, 1396)
|
690 Participants
|
735 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Leukocytes, low (n=1457, 1471)
|
27 Participants
|
26 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Basophils (absolute), high (n=1448, 1465)
|
2 Participants
|
4 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Eosinophils (absolute), high (n=1448, 1465)
|
43 Participants
|
60 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Lymphocytes (absolute), low (n=1448, 1465)
|
203 Participants
|
215 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Lymphocytes (absolute), high (n=1448, 1465)
|
1 Participants
|
0 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Monocytes (absolute), high (n=1448, 1465)
|
5 Participants
|
2 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Neutrophils (absolute), low (n=1448, 1465)
|
5 Participants
|
2 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Alkaline phosphatase (ALP), high (n=1465, 1476)
|
15 Participants
|
31 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Aspartate aminotransferase (AST) , high (n=1459,14
|
34 Participants
|
26 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Bilirubin, direct (high) (n=1447,1457)
|
87 Participants
|
76 Participants
|
|
Summary of Laboratory Marked Abnormalities on Hematology and Liver and Kidney Function Test Results During the Treatment Period (Patients With Available Measurements)
Blood urea nitrogen (BUN) (high)(n=1447,1458)
|
15 Participants
|
17 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (±5 days) of follow-upPopulation: All participants who received at least 1 dose of study drug. n=number of participants with available measurements
preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. Calcium, total (mg/dL): \<0.8\*LLN or \>1.2\*ULN, or if preRx\<LLN use \<0.75\*preRx or \>ULN if preRx \>ULN use \>1.25\*preRx or \<LLN; chloride, serum (mEq/L): \<0.9\*LLN or \>1.1\*ULN, or if preRx\<LLN use \<0.9\*preRx or \>ULN if preRx\>ULN use \>1.1\*preRx or \<LLN; bicarbonate (mEq/L): \<0.75\*LLN or \>1.25\*ULN, or if preRx \< LLN use \<0.75\*preRx or \>ULN if preRx \>ULN use \>1.25\*preRx or \< LLN; potassium, serum (mEq/L): \<0.9\* LLN or \>1.1\*ULN, or if preRx\<LLN use \<0.9 \*preRx or \>ULN if preRx\>ULN use \>1.1\*preRx or \<LLN; sodium, serum (mEq/L): \<0.95\*LLN or \>1.05\*ULN, or if preRx \<LLN use \<0.95\*preRx or \>ULN if preRx\>ULN use \>1.05\*preRx or \<LLN; protein, total (g/dL): \<0.9\*LLN or \>1.1\*ULN, or if preRx \<LLN use 0.9\*preRx or \>ULN if preRx \>ULN use 1.1\*preRx or \<LLN; CK (U/L): \>5\*ULN; uric acid (mg/dL): \>1.5\*ULN, or if preRx \>ULN use \>2\*preRx; glucose, fasting serum (mg/dL): \<0.8\*LLN or \>1.5\*ULN, or if preRx \<LLN use \<0.8\*preRx or \>ULN.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=1501 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=1508 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Calcium, total (low) (n=1447, 1457)
|
5 Participants
|
9 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Chloride, serum (low)(n=1442, 1454)
|
1 Participants
|
0 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Bicarbonate (low) (n=1435, 1447)
|
0 Participants
|
3 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Potassium, serum (low) (n=1438, 1453)
|
38 Participants
|
41 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Potassium, serum (high)(n=1438, 1453)
|
34 Participants
|
40 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Sodium, serum (low) (n=1442, 1454)
|
5 Participants
|
10 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Sodium, serum (high) (n=1442, 1454)
|
1 Participants
|
0 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Glucose, fasting serum (low) (n=715, 713)
|
8 Participants
|
1 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Glucose, fasting serum (high) (n=715, 713)
|
46 Participants
|
25 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Protein, total (low) (n=1447, 1457
|
223 Participants
|
243 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Creatine kinase (CK) (high) (n=1463, 1476)
|
66 Participants
|
65 Participants
|
|
Summary of Laboratory Marked Abnormalities in Electrolyte and Other Clinical Test Results During the Treatment Period (Patients With Available Measurements)
Uric acid (high) (n=1446, 1458)
|
1 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Randomization to Days 2, 3, 4, and 12 (±2 days) and at Days 42 and 72 (± 5 days) of follow-upPopulation: All participants who received at least 1 dose of study drug. n=number of participants with available measurements
preRX=pretreatment. Blood, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; glucose, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; protein, urine: If missing preRx use ≥ 2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; Red blood cells , urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4; white blood cells, urine: If missing preRx use ≥2, or if value ≥4, or if preRx=0 or 0.5 use ≥2, or if preRx=1 use ≥3, or if preRx=2 or 3 use ≥4.
Outcome measures
| Measure |
Apixaban, 2.5 mg BID + Placebo
n=1501 Participants
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD + Placebo
n=1508 Participants
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis)
Glucose, urine (high) (n=1421, 1429)
|
160 Participants
|
154 Participants
|
|
Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis)
White blood cells, urine (high)(n=441, 386)
|
101 Participants
|
102 Participants
|
|
Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis)
Blood, urine (high) (n=1421, 1430)
|
169 Participants
|
113 Participants
|
|
Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis)
Protein, urine (high) (n=1421, 1430)
|
60 Participants
|
89 Participants
|
|
Summary of Laboratory Marked Abnormalities in Urinalysis Results During the Treatment Period-Treated Subjects With Available Measurements (Urinalysis)
Red blood cells, urine (high) (n=441, 385)
|
133 Participants
|
116 Participants
|
Adverse Events
Apixiban, 2.5 mg BID Plus Placebo
Serious events: 72 serious events
Other events: 295 other events
Deaths: 0 deaths
Enoxaparin, 40 mg QD Plus Placebo
Serious events: 88 serious events
Other events: 342 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Apixiban, 2.5 mg BID Plus Placebo
n=1501 participants at risk
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=1508 participants at risk
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Investigations
Creatinine renal clearance decreased
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Nervous system disorders
Hypokinesia
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Overdose
|
0.07%
1/1501
|
0.07%
1/1508
|
|
Renal and urinary disorders
Renal failure acute
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Suture related complication
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Cardiac disorders
Atrial flutter
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Nervous system disorders
Cerebrovascular accident
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.00%
0/1501
|
0.13%
2/1508
|
|
Vascular disorders
Hypertensive crisis
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Cardiac disorders
Myocardial ischaemia
|
0.07%
1/1501
|
0.00%
0/1508
|
|
General disorders
Oedema peripheral
|
0.13%
2/1501
|
0.13%
2/1508
|
|
Infections and infestations
Subcutaneous abscess
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Vascular disorders
Wound haemorrhage
|
0.13%
2/1501
|
0.00%
0/1508
|
|
Blood and lymphatic system disorders
Anaemia
|
0.13%
2/1501
|
0.07%
1/1508
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Nervous system disorders
Cerebral infarction
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Device dislocation
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Infections and infestations
Erysipelas
|
0.13%
2/1501
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Foreign body trauma
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Vascular disorders
Hypertension
|
0.07%
1/1501
|
0.00%
0/1508
|
|
General disorders
Injection site extravasation
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Investigations
Platelet count increased
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.00%
0/1501
|
0.13%
2/1508
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.07%
1/1501
|
0.00%
0/1508
|
|
General disorders
Pyrexia
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory acidosis
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Nervous system disorders
Senile dementia
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Vascular disorders
Varicose vein
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Wound
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Investigations
Body temperature increased
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/1501
|
0.13%
2/1508
|
|
Nervous system disorders
Cerebrovascular insufficiency
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Hepatobiliary disorders
Hepatitis
|
0.13%
2/1501
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/1501
|
0.13%
2/1508
|
|
Infections and infestations
Respiratory tract infection viral
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Cardiac disorders
Angina pectoris
|
0.07%
1/1501
|
0.07%
1/1508
|
|
Infections and infestations
Arthritis bacterial
|
0.07%
1/1501
|
0.07%
1/1508
|
|
Cardiac disorders
Bradycardia
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Infections and infestations
Bronchitis
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Infections and infestations
Bronchopneumonia
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/1501
|
0.07%
1/1508
|
|
General disorders
Death
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Fall
|
0.07%
1/1501
|
0.07%
1/1508
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Operative haemorrhage
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Investigations
Oxygen saturation decreased
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Infections and infestations
Post procedural infection
|
0.00%
0/1501
|
0.13%
2/1508
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.33%
5/1501
|
0.07%
1/1508
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Infections and infestations
Wound sepsis
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Cardiac disorders
Acute left ventricular failure
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.07%
1/1501
|
0.07%
1/1508
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/1501
|
0.07%
1/1508
|
|
General disorders
Catheter related complication
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Infections and infestations
Device related infection
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Gastrointestinal disorders
Gastritis
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Investigations
Haemoglobin decreased
|
0.07%
1/1501
|
0.07%
1/1508
|
|
Vascular disorders
Haemorrhage
|
0.27%
4/1501
|
0.20%
3/1508
|
|
Vascular disorders
Hypotension
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Incision site haemorrhage
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Intra-abdominal haematoma
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Cardiac disorders
Palpitations
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Infections and infestations
Postoperative wound infection
|
0.20%
3/1501
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Infections and infestations
Tuberculosis
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Cardiac disorders
Atrial fibrillation
|
0.07%
1/1501
|
0.33%
5/1508
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Vascular disorders
Haematoma
|
0.00%
0/1501
|
0.13%
2/1508
|
|
Investigations
Hepatic enzyme increased
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.07%
1/1501
|
0.07%
1/1508
|
|
Infections and infestations
Localised infection
|
0.00%
0/1501
|
0.13%
2/1508
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.13%
2/1501
|
0.00%
0/1508
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Vascular disorders
Deep vein thrombosis
|
0.73%
11/1501
|
1.5%
22/1508
|
|
Musculoskeletal and connective tissue disorders
Haemarthrosis
|
0.00%
0/1501
|
0.13%
2/1508
|
|
Hepatobiliary disorders
Hepatic ischaemia
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
0.07%
1/1501
|
0.07%
1/1508
|
|
General disorders
Multi-organ failure
|
0.00%
0/1501
|
0.07%
1/1508
|
|
Infections and infestations
Staphylococcal infection
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.07%
1/1501
|
0.00%
0/1508
|
|
Infections and infestations
Wound infection
|
0.13%
2/1501
|
0.27%
4/1508
|
Other adverse events
| Measure |
Apixiban, 2.5 mg BID Plus Placebo
n=1501 participants at risk
Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
|
Enoxaparin, 40 mg QD Plus Placebo
n=1508 participants at risk
Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
4.9%
73/1501
|
5.1%
77/1508
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
77/1501
|
5.8%
88/1508
|
|
Gastrointestinal disorders
Nausea
|
6.8%
102/1501
|
8.0%
120/1508
|
|
Vascular disorders
Deep vein thrombosis
|
6.1%
92/1501
|
8.6%
130/1508
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication
- Publication restrictions are in place
Restriction type: OTHER