Multi-center Study to Evaluate the Safety of Apixaban (BMS-562247) in Indian Subjects Undergoing Elective Total Knee Replacement or Total Hip Replacement Surgery

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01884337
• Collaborator: Pfizer (Industry)
• Enrollment: 557
• Locations: 20
• Arm: 1
• Actual Duration (Months): 38.4
• Patients Per Site: 27.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The primary purpose of this protocol is to evaluate the safety of Apixaban in prophylaxis of Venous Thromboembolism (VTE) in Indian patients undergoing elective total knee or hip replacement

Condition or Disease	Intervention/Treatment	Phase
Anticoagulation	Drug: Apixaban	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 557 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IV, Open-Label, Multi-center Study to Evaluate the Safety of Apixaban in Indian Subjects Undergoing Elective Total Knee Replacement or Total Hip Replacement Surgery
• Actual Study Start Date: Mar 24, 2015
• Actual Primary Completion Date: Jun 4, 2018
• Actual Study Completion Date: Jun 4, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apixaban (2.5 mg) Apixaban 2.5 mg tablets by mouth twice daily, 12 days for TKR subjects or 35 days for THR subjects	Drug: Apixaban; Other Names: Eliquis BMS-562247

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Composite of International Society on Thrombosis and Haemostasis (ISTH) Major Bleeding/Clinically Relevant Non-major Bleeding (CRNM) While Undergoing Elective TKR or THR at the End of Treatment + 2 Days [2 weeks + 2 days for TKR, 5 weeks + 2 days for THR]

   TKR = Total knee replacement; THR = Total hip replacement. ISTH major bleeding is 1) Fatal or 2) Bleeding in a critical organ, such as brain, spine, eye, retroperitoneum, joint, heart sac, or skeletal muscle (and resulting in compartment syndrome), or 3) Bleeding that results in a fall of hemoglobin of 2 g/dL or more or transfusion of 2 units or more of packed red cells or whole blood within 24 hours. CRNM bleeding is bleeding that 1) Is clinically acute and overt 2) Does not satisfy criteria as a major bleed but requires medical intervention, such as a visit to a physician's office, emergency room, or urgent care center for epistaxis

Secondary Outcome Measures

1. Number of Participants With Composite of Venous Thromboembolism (VTE)/All Cause Death at the End of Treatment + 2 Days [2 weeks + 2 days for TKR, 5 weeks + 2 days for THR]

   VTE is the combination of deep vein thrombosis and non-fatal pulmonary embolism.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥18 years

• Subjects undergoing elective total knee or hip replacement or a revision of at least one component of a total knee or hip replacement

Exclusion Criteria:

• Women who are pregnant or breastfeeding

• Known or suspected, acquired or bleeding or coagulation disorder in the subject or a first degree relative

• Active bleeding or at high risk for bleeding.

• Brain, spinal, ophthalmologic, or major surgery or trauma within the past 90 days other than the elective knee/hip surgery

• Active hepatobiliary disease

• Hemoglobin <9 g/dL

• Platelet count <100,000/mm3

• Creatinine clearance <30 mL/min

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Kozhikode	Kerala	India	673008
2	Local Institution	Ahmedabad		India	380015
3	Local Institution	Ahmedabad		India	380016
4	Local Institution	Ahmedabad		India	380060
5	Local Institution	Alappuzha		India	688005
6	Local Institution	Aurangabad		India	431003
7	Local Institution	Bangalore		India	560054
8	Local Institution	Chandigarh		India	160012
9	Local Institution	Chennai		India	600010
10	Local Institution	Delhi		India	110029
11	Local Institution	Hyderabad		India	500034
12	Local Institution	Kerala		India	695011
13	Local Institution	Lucknow		India	226003
14	Local Institution	Mohali		India	160062
15	Local Institution	Mumbai		India	400 022
16	Local Institution	Nagpur		India	440003
17	Local Institution	Pune		India	411001
18	Local Institution	Pune		India	411004
19	Local Institution	Pune		India	411005
20	Local Institution	Pune		India	411013

Sponsors and Collaborators

• Bristol-Myers Squibb
• Pfizer

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol - Jul 22, 2014
• Statistical Analysis Plan - Jul 2, 2018

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01884337
• Other Study ID Numbers: CV185-158
• First Posted: Jun 24, 2013
• Last Update Posted: Nov 29, 2019
• Last Verified: Nov 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Apixaban

Study Results

Participant Flow

Recruitment Details	This study was conducted in an Indian orthopedic population.
Pre-assignment Detail	557 participants were enrolled, of whom 498 were treated. Of the 59 who were not treated, 42 no longer met study criteria, 6 withdrew consent, 11 due to other reasons. Of the 326 who started Total Knee Replacement, 324 continued into follow-up period and of the 172 who started Total Hip Replacement, 170 continued into follow-up period.

Arm/Group Title	Total Knee Replacement (TKR)	Total Hip Replacement (THR)
Arm/Group Description	Oral administration of apixaban 2.5 mg twice daily (BID) for 2 weeks	Oral administration of apixaban 2.5 mg twice daily (BID) for 5 weeks
Period Title: Treatment
STARTED	326	172
Continuing Into Follow-up Period	324	171
COMPLETED	322	170
NOT COMPLETED	4	2
Period Title: Treatment
STARTED	324	171
COMPLETED	323	170
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Total Knee Replacement (TKR)	Total Hip Replacement (THR)	Total
Arm/Group Description	Oral administration of apixaban 2.5 mg twice daily (BID) for 2 weeks	Oral administration of apixaban 2.5 mg twice daily (BID) for 5 weeks	Total of all reporting groups
Overall Participants	326	172	498
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.7 (9.59)	41.7 (13.30)	54.1 (11.01)
Sex: Female, Male (Count of Participants)
Female	237 72.7%	53 30.8%	290 58.2%
Male	89 27.3%	119 69.2%	208 41.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 0.9%	9 5.2%	12 2.4%
Not Hispanic or Latino	322 98.8%	163 94.8%	485 97.4%
Unknown or Not Reported	1 0.3%	0 0%	1 0.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	326 100%	172 100%	498 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Composite of International Society on Thrombosis and Haemostasis (ISTH) Major Bleeding/Clinically Relevant Non-major Bleeding (CRNM) While Undergoing Elective TKR or THR at the End of Treatment + 2 Days
Description	TKR = Total knee replacement; THR = Total hip replacement. ISTH major bleeding is 1) Fatal or 2) Bleeding in a critical organ, such as brain, spine, eye, retroperitoneum, joint, heart sac, or skeletal muscle (and resulting in compartment syndrome), or 3) Bleeding that results in a fall of hemoglobin of 2 g/dL or more or transfusion of 2 units or more of packed red cells or whole blood within 24 hours. CRNM bleeding is bleeding that 1) Is clinically acute and overt 2) Does not satisfy criteria as a major bleed but requires medical intervention, such as a visit to a physician's office, emergency room, or urgent care center for epistaxis
Time Frame	2 weeks + 2 days for TKR, 5 weeks + 2 days for THR

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug during the Treatment Period

Arm/Group Title	Total Knee Replacement (TKR)	Total Hip Replacement (THR)
Arm/Group Description	Oral administration of apixaban 2.5 mg twice daily (BID) for 2 weeks	Oral administration of apixaban 2.5 mg twice daily (BID) for 5 weeks
Measure Participants	326	172
Major Bleeding	0 0%	0 0%
Clinically Relevant Non-Major Bleeding	0 0%	1 0.6%
Major or Clinically Relevant Non-Major Bleeding	0 0%	1 0.6%
Any Bleeding	0 0%	1 0.6%

2. Secondary Outcome

Title	Number of Participants With Composite of Venous Thromboembolism (VTE)/All Cause Death at the End of Treatment + 2 Days
Description	VTE is the combination of deep vein thrombosis and non-fatal pulmonary embolism.
Time Frame	2 weeks + 2 days for TKR, 5 weeks + 2 days for THR

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug

Arm/Group Title	Total Knee Replacement (TKR)	Total Hip Replacement (THR)
Arm/Group Description	Oral administration of apixaban 2.5 mg twice daily (BID) for 2 weeks	Oral administration of apixaban 2.5 mg twice daily (BID) for 5 weeks
Measure Participants	326	172
Count of Participants [Participants]	1 0.3%	1 0.6%

Adverse Events

Time Frame	AEs are assessed from Day 1 through Day 42 +/- 2 days for Total Knee Replacement Participants; AEs are assessed from Day 1 through Day 65 +/-2 days for Total Hip Replacement Participants.
Arm/Group Title	TOTAL KNEE REPLACEMENT (TKR)		TOTAL HIP REPLACEMENT (THR)
Arm/Group Description	Oral administration of apixaban 2.5 mg twice daily (BID) for 2 weeks		Oral administration of apixaban 2.5 mg twice daily (BID) for 5 weeks
All Cause Mortality
	TOTAL KNEE REPLACEMENT (TKR)		TOTAL HIP REPLACEMENT (THR)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/326 (0%)		0/172 (0%)
Serious Adverse Events
	TOTAL KNEE REPLACEMENT (TKR)		TOTAL HIP REPLACEMENT (THR)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/326 (0.6%)		0/172 (0%)
Blood and lymphatic system disorders
Anaemia	1/326 (0.3%)		0/172 (0%)
Ear and labyrinth disorders
Vertigo	1/326 (0.3%)		0/172 (0%)
Vascular disorders
Deep vein thrombosis	1/326 (0.3%)		0/172 (0%)
Other (Not Including Serious) Adverse Events
	TOTAL KNEE REPLACEMENT (TKR)		TOTAL HIP REPLACEMENT (THR)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/326 (7.1%)		6/172 (3.5%)
Injury, poisoning and procedural complications
Incision site pain	23/326 (7.1%)		6/172 (3.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.