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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00423319




Registration number
NCT00423319
Ethics application status
Date submitted
17/01/2007
Date registered
18/01/2007
Date last updated
14/05/2014

Titles & IDs
Public title
Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)
Scientific title
A Phase 3 Randomized, Double-blind, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Safety and Efficacy of Apixaban in Subjects Undergoing Elective Total Hip Replacement Surgery (The Advance-3 Study Apixaban Dosed Orally Versus Anticoagulation With Injectable Enoxaparin to Prevent Venous Thromboembolism)
Secondary ID [1] 0 0
CV185-035
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
Treatment: Drugs - Apixaban
Treatment: Drugs - Enoxaparin-matching placebo
Treatment: Drugs - Apixaban-matching placebo

Active comparator: Apixaban, 2.5 mg BID plus placebo - Participants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)

Experimental: Enoxaparin, 40 mg QD plus placebo - Participants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID


Treatment: Drugs: Enoxaparin
Subcutaneous, 40 mg, once daily, 5 weeks

Treatment: Drugs: Apixaban
Oral tablets, 2.5 mg, twice daily, 5weeks

Treatment: Drugs: Enoxaparin-matching placebo
Administered as injection

Treatment: Drugs: Apixaban-matching placebo
Administered as oral tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period
Timepoint [1] 0 0
Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Secondary outcome [1] 0 0
Rate of Composite of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During Intended Treatment Period
Timepoint [1] 0 0
Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Secondary outcome [2] 0 0
Rates of Adjudicated All-cause Death, VTE-related Death, Pulmonary Embolism (PE), Nonfatal PE, Deep Vein Thrombosis (DVT) (Symptomatic and Asymptomatic), Symptomatic and Asymptomatic Proximal and Distal DVT During the Intended Treatment Period
Timepoint [2] 0 0
Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose
Secondary outcome [3] 0 0
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), Major or CRNM, and Any Bleeding During the Treatment Period
Timepoint [3] 0 0
First dose of study drug (presurgery) through 2 days after the last dose of study drug
Secondary outcome [4] 0 0
Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), and Death as Outcome
Timepoint [4] 0 0
First dose of study drug (presurgery) through 30 days after the last dose of study drug
Secondary outcome [5] 0 0
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period
Timepoint [5] 0 0
First dose of study drug (presurgery) through 2 days after the last dose of study drug
Secondary outcome [6] 0 0
Number of Participants With a Bleeding-related Adverse Events During the Treatment Period (Continued)
Timepoint [6] 0 0
First dose of study drug (presurgery) through 2 days after the last dose of study drug
Secondary outcome [7] 0 0
Number of Participants With a Bleeding-related Adverse Event During the Treatment Period (Continued)
Timepoint [7] 0 0
First dose of study drug (presurgery) through 2 days after the last dose of study drug
Secondary outcome [8] 0 0
Number of Participants With Neurologic Adverse Events With Onset During the Treatment Period
Timepoint [8] 0 0
First dose of study drug (presurgery) through 2 days after the last dose of study drug
Secondary outcome [9] 0 0
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period
Timepoint [9] 0 0
First dose of study drug (presurgery) through 2 days after the last dose of study drug
Secondary outcome [10] 0 0
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Timepoint [10] 0 0
First dose of study drug (presurgery) through 2 days after the last dose of study drug
Secondary outcome [11] 0 0
Number of Participants With Marked Abnormalities (MA) in Clinical Laboratory Test Results During the Treatment Period (Continued)
Timepoint [11] 0 0
First dose of study drug (presurgery) through 2 days after the last dose of study drug
Secondary outcome [12] 0 0
Number of Participants With Adverse Events Related to Elevations in Liver Function Test Results With Onset During the Treatment Period
Timepoint [12] 0 0
First dose of study drug (presurgery) through 30 days after the last dose of study drug
Secondary outcome [13] 0 0
Rates of Adjudicated Myocardial Infarction (MI)/Stroke, MI, Stroke, and Thrombocytopenia During the Intended Treatment Period
Timepoint [13] 0 0
Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose

Eligibility
Key inclusion criteria
Key Inclusion Criteria

* Patients undergoing elective unilateral total hip replacement or a revision of at least 1 component of a total hip replacement.
* Patients who were willing and able to undergo bilateral ascending contrast venography
* Either sex, any race, 18 years and older

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Known or suspected bleeding or coagulation disorder in the patient or his or her first-degree relative
* Known or suspected history of heparin-induced thrombocytopenia
* Known coagulopathy
* Active bleeding or at high risk for bleeding
* Brain, spinal, ophthalmologic, or major surgery or trauma within the past 90 days
* Active hepatobiliary disease
* Alcohol and/or substance abuse within the past year
* Any condition for which surgery or administration of an anticoagulant is contraindicated
* Two consecutive blood pressure readings within 15 to 30 minutes with supine systolic blood pressure >180 mm Hg or supine diastolic blood pressure >105 mm Hg
* Clinically significant laboratory abnormalities at the enrollment visit:
* Hemoglobin <10 g/dL
* Platelet count <100,000/mm^3
* Creatinine clearance <30 mL/min, as estimated by the method of Cockcroft and Gault
* Alanine aminotransferase or aspartate aminotransferase >2*upper limit of normal or a total bilirubin = 1.5*1 (unless an alternative causative factor such as Gilbert's syndrome was identified)
* Need for ongoing treatment with a parenteral or oral anticoagulant (eg, subjects with mechanical valves, warfarin eligible atrial fibrillation)
* Current use of dextrans or fibrinolytics
* Treatment with medications affecting coagulation or platelet function

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
1/03/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2009
Sample size
Target
Accrual to date
Final
5407
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - Camperdown
Recruitment hospital [2] 0 0
Local Institution - Kogarah
Recruitment hospital [3] 0 0
Local Institution - Lismore
Recruitment hospital [4] 0 0
Local Institution - Southport
Recruitment hospital [5] 0 0
Local Institution - Bedford Park
Recruitment hospital [6] 0 0
Local Institution - Box Hill
Recruitment hospital [7] 0 0
Local Institution - Malvern
Recruitment hospital [8] 0 0
Local Institution - Windsor
Recruitment hospital [9] 0 0
Local Institution - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2480 - Lismore
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
3144 - Malvern
Recruitment postcode(s) [8] 0 0
3181 - Windsor
Recruitment postcode(s) [9] 0 0
6000 - 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
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
Country [11] 0 0
Belgium
State/province [11] 0 0
Antwerp
Country [12] 0 0
Belgium
State/province [12] 0 0
Brasschaat
Country [13] 0 0
Belgium
State/province [13] 0 0
Genk
Country [14] 0 0
Belgium
State/province [14] 0 0
Hasselt
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
China
State/province [19] 0 0
Beijing
Country [20] 0 0
China
State/province [20] 0 0
Guangdong
Country [21] 0 0
China
State/province [21] 0 0
Shandong
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China
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Shanghai
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Denmark
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Amager
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Denmark
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Frederiksberg
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Denmark
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Herlev
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Horsholm
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Denmark
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Hvidovre
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Denmark
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Kobenhavn Nv
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Denmark
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Silkeborg
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France
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Nice
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France
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Paris
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France
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Saint Etienne
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France
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Saint-Saulve
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Germany
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Frankfurt / Main
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Germany
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Frankfurt
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Germany
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Rheinfelden
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Hungary
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Budapest
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Hungary
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Kecskemet
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Hungary
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Szeged
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Hungary
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Szolnok
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Gujarat
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Uttar Prsdesh
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Holon
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Aguascalientes
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Gjettum
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Lillehammer
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Tynset
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Gdansk
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Szczecin
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Warszawa
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Wroclaw
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Romania
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Bucharest
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Romania
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Cluj Napoca
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Russian Federation
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Chelyabinsk
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Kazan
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Moscow
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Saint Petersburg
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Samara
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Russian Federation
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St.Petersburg
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Russian Federation
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Yaroslavl
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Spain
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Badalona-Barcelone
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Spain
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Barcelona
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Sweden
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Sweden
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Stockholm
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Ukraine
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Cherkassy
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Ukraine
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Chernivtsy
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Ukraine
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Dnipropetrovsk
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Ukraine
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Ivano-Frankivsk
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Ukraine
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Kyiv
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Ukraine
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Sevastopol
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United Kingdom
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Greater London
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Lancashire
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Surrey

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00423319