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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00371683




Registration number
NCT00371683
Ethics application status
Date submitted
30/08/2006
Date registered
4/09/2006
Date last updated
30/12/2015

Titles & IDs
Public title
Study of Apixaban for the Prevention of Thrombosis-related Events Following Knee Replacement Surgery
Scientific title
A Phase 3 Randomized, Double-Blind Active-Controlled (Enoxaparin), Parallel-Group, Multi-Center Study to Evaluate the Safety and Efficacy of Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement Surgery
Secondary ID [1] 0 0
CV185-034
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Deep Vein Thrombosis 0 0
Pulmonary Embolism 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Blood 0 0 0 0
Clotting disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Enoxaparin + Placebo
Treatment: Drugs - Apixaban + Placebo

Active comparator: A1 - + placebo

Experimental: A2 - + placebo


Treatment: Drugs: Enoxaparin + Placebo
Syringes + tablets, Subcutaneous + Oral, 30mg, twice daily, 12 day treatment period

Treatment: Drugs: Apixaban + Placebo
Tablet + Syringes, Oral + subcutaneous, 2.5 mg, twice daily, 12 day treatment period
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects
Timepoint [1] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Primary outcome [2] 0 0
Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population
Timepoint [2] 0 0
First dose of study drug to last dose, plus 2 days post last dose
Primary outcome [3] 0 0
Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period
Timepoint [3] 0 0
Last dose of study drug to Day 72 (60 days)
Secondary outcome [1] 0 0
Event Rate of Composite of Adjudicated Proximal DVT, Non-Fatal PE and All-Cause Death With Onset During the Intended Treatment Period PE and All-cause Death During the Intended Treatment Period
Timepoint [1] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [2] 0 0
Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period
Timepoint [2] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [3] 0 0
Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period
Timepoint [3] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [4] 0 0
Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period
Timepoint [4] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [5] 0 0
Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period
Timepoint [5] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [6] 0 0
Event Rate for Participants With All-Cause Death During the Intended Treatment Period
Timepoint [6] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [7] 0 0
Event Rate for Participants With VTE-Related Death With Onset During the Intended Treatment Period
Timepoint [7] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [8] 0 0
Event Rate for Participants With Symptomatic VTE/ All-Cause Death With Onset During the Intended Treatment Period
Timepoint [8] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [9] 0 0
Event Rate for Participants With Symptomatic VTE/ VTE-Related Death With Onset During the Intended Treatment Period
Timepoint [9] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [10] 0 0
Event Rate for Participants With VTE/Major Bleeding/All-Cause Death With Onset During the Intended Treatment Period
Timepoint [10] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [11] 0 0
Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period
Timepoint [11] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [12] 0 0
Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period
Timepoint [12] 0 0
From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
Secondary outcome [13] 0 0
Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period
Timepoint [13] 0 0
From first dose to last dose, plus 2 days (12 days, plus 2)
Secondary outcome [14] 0 0
Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period
Timepoint [14] 0 0
Post last dose of study drug to Day 72 (60 days)
Secondary outcome [15] 0 0
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population
Timepoint [15] 0 0
First dose to last dose, plus 2 days for AEs (12 + 2 days) or plus 30 days for SAEs (12 + 30 days)
Secondary outcome [16] 0 0
Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period
Timepoint [16] 0 0
Baseline to last dose of study drug, plus 2 days
Secondary outcome [17] 0 0
Mean Change From Baseline in Heart Rate During the Treatment Period
Timepoint [17] 0 0
Baseline to last dose of study drug, plus 2 days
Secondary outcome [18] 0 0
Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period
Timepoint [18] 0 0
First dose to last dose of study drug (12 days), plus 2 days
Secondary outcome [19] 0 0
Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period
Timepoint [19] 0 0
First dose to last dose of study drug (12 days), plus 2 days
Secondary outcome [20] 0 0
Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period
Timepoint [20] 0 0
First dose to last dose of study drug (12 days), plus 2 days
Secondary outcome [21] 0 0
Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period
Timepoint [21] 0 0
First dose to last dose of study drug (12 days), plus 2 days

Eligibility
Key inclusion criteria
Key

* Men and non-pregnant, non-breastfeeding women
* 18 years or older
* Scheduled for knee replacement surgery

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* hereditary or acquired bleeding disorders
* clotting disorders
* bleeding or high risk for bleeding
* drugs that affect bleeding or coagulation
* need for ongoing parenteral or oral anticoagulation

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2008
Sample size
Target
Accrual to date
Final
3608
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - Garran
Recruitment hospital [2] 0 0
Local Institution - Camperdown
Recruitment hospital [3] 0 0
Local Institution - Caringbah
Recruitment hospital [4] 0 0
Local Institution - Lismore
Recruitment hospital [5] 0 0
Local Institution - Gold Coast
Recruitment hospital [6] 0 0
Local Institution - Adelaide
Recruitment hospital [7] 0 0
Local Institution - Bedford Park
Recruitment hospital [8] 0 0
Local Institution - Box Hill
Recruitment hospital [9] 0 0
Local Institution - Windsor
Recruitment hospital [10] 0 0
Local Institution - Perth
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
NSW 2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2229 - Caringbah
Recruitment postcode(s) [4] 0 0
2480 - Lismore
Recruitment postcode(s) [5] 0 0
4215 - Gold Coast
Recruitment postcode(s) [6] 0 0
5011 - Adelaide
Recruitment postcode(s) [7] 0 0
5042 - Bedford Park
Recruitment postcode(s) [8] 0 0
3128 - Box Hill
Recruitment postcode(s) [9] 0 0
3181 - Windsor
Recruitment postcode(s) [10] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Idaho
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Argentina
State/province [12] 0 0
Buenos Aires
Country [13] 0 0
Argentina
State/province [13] 0 0
Cordoba
Country [14] 0 0
Brazil
State/province [14] 0 0
Parana
Country [15] 0 0
Brazil
State/province [15] 0 0
Rio Grande Do Sul
Country [16] 0 0
Brazil
State/province [16] 0 0
Sao Paulo
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Prince Edward Island
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
Denmark
State/province [21] 0 0
Horsholm
Country [22] 0 0
Denmark
State/province [22] 0 0
Kopenhamn S
Country [23] 0 0
Hungary
State/province [23] 0 0
Kecskemet
Country [24] 0 0
Hungary
State/province [24] 0 0
Szekesfehervar
Country [25] 0 0
Hungary
State/province [25] 0 0
Szolnok
Country [26] 0 0
Israel
State/province [26] 0 0
Afula
Country [27] 0 0
Israel
State/province [27] 0 0
Beer-Sheva
Country [28] 0 0
Israel
State/province [28] 0 0
Haifa
Country [29] 0 0
Israel
State/province [29] 0 0
Holon
Country [30] 0 0
Israel
State/province [30] 0 0
Kfar-Saba
Country [31] 0 0
Israel
State/province [31] 0 0
Petach-Tikva
Country [32] 0 0
Israel
State/province [32] 0 0
Rehovot
Country [33] 0 0
Israel
State/province [33] 0 0
Zerifin
Country [34] 0 0
Mexico
State/province [34] 0 0
Baja California
Country [35] 0 0
Mexico
State/province [35] 0 0
Distrito Federal
Country [36] 0 0
Mexico
State/province [36] 0 0
Jalisco
Country [37] 0 0
Mexico
State/province [37] 0 0
Nuevo Leon
Country [38] 0 0
Mexico
State/province [38] 0 0
Tamaulipas
Country [39] 0 0
Mexico
State/province [39] 0 0
Veracruz
Country [40] 0 0
Mexico
State/province [40] 0 0
Yucatan
Country [41] 0 0
Mexico
State/province [41] 0 0
Chihuahua
Country [42] 0 0
Poland
State/province [42] 0 0
Bialystok
Country [43] 0 0
Poland
State/province [43] 0 0
Krakow
Country [44] 0 0
Poland
State/province [44] 0 0
Lodz
Country [45] 0 0
Poland
State/province [45] 0 0
Lublin
Country [46] 0 0
Poland
State/province [46] 0 0
Szczecin
Country [47] 0 0
Poland
State/province [47] 0 0
Warszawa
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Moscow
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Samara
Country [50] 0 0
Russian Federation
State/province [50] 0 0
St. Petersburg
Country [51] 0 0
Sweden
State/province [51] 0 0
Goteborg
Country [52] 0 0
Turkey
State/province [52] 0 0
Adana
Country [53] 0 0
Turkey
State/province [53] 0 0
Bursa
Country [54] 0 0
Turkey
State/province [54] 0 0
Mersin
Country [55] 0 0
Turkey
State/province [55] 0 0
Trabzon

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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 after knee replacement surgery and to learn how apixaban compares to enoxaparin (Lovenox®) for preventing these clots. The safety of apixaban will also be studied.
Trial website
https://clinicaltrials.gov/study/NCT00371683
Trial related presentations / publications
Jamieson MJ, Byon W, Dettloff RW, Crawford M, Gargalovic PS, Merali SJ, Onorato J, Quintero AJ, Russ C. Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data. Am J Cardiovasc Drugs. 2022 Nov;22(6):615-631. doi: 10.1007/s40256-022-00524-x. Epub 2022 May 16.
Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009 Aug 6;361(6):594-604. doi: 10.1056/NEJMoa0810773. Erratum In: N Engl J Med. 2009 Oct 29;361(18):1814.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00371683