ADVANCE-1 trial

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Systematic review and meta-analysis

This trial is included in the following systematic reviews and meta-analyses:

DVT prophylaxis - anticoagulant - orthopedic surgery

DVT prophylaxis - direct factor Xa inhibitors - all type of patients

DVT prophylaxis - new anticoagulants - all type of patients

DVT prophylaxis - new anticoagulants - elective major knee surgery

ADVANCE 2 (CV185-047), 2010 - apixaban vs enoxaparin

WATCH (warfarin vs aspirin), 2009 - warfarin vs aspirin

RECORD 4, 2009 - rivaroxaban vs enoxaparin

RE-MOBILIZE (150mg), 2008 - dabigatran 150mg vs enoxaparin

RECORD 3, 2008 - rivaroxaban vs enoxaparin

RECORD 2, 2008 - extended rivaroxaban vs enoxaparin

RE-MOBILIZE (220mg), 2008 - dabigatran 220mg vs enoxaparin

ADVANCE-1, 2008 - apixaban vs enoxaparin

RECORD 1, 2008 - extended rivaroxaban vs extended enoxaparin

RE-NOVATE (220mg), 2007 - dabigatran 220mg vs enoxaparin

RE-MODEL (220mg), 2007 - dabigatran 220mg vs enoxaparin

RE-NOVATE (150mg), 2007 - dabigatran 150mg vs enoxaparin

RE-MODEL (150mg), 2007 - dabigatran 150mg vs enoxaparin

HELAS (warfarin vs aspirin), 2006 - warfarin vs aspirin

ODIXa-HIP 10mg, 2006 - rivaroxaban vs enoxaparin

ODIXa-KNEE, 2005 - rivaroxaban vs enoxaparin

BISTRO II (225mg bid), 2005 - dabigatran 450mg vs enoxaparin

NASPEAF (triflusal+coumadin medium dose vs triflusal), 2004 - triflusal+coumadin medium dose vs triflusal

NASPEAF (triflusal + coumadin medium dose vs coumadin standard dose), 2004 - triflusal+coumadin medium dose vs coumadin standard dose

WASH (warfarin), 2004 - warfarin vs no treatment

Samama, 2001 - Acenocoumarol vs Reviparin

Fitzgerald, 2001 - Warfarin vs Enoxaparin

Hull, 2000 - Warfarin vs Dalteparin

Colwell, 1999 - Warfarin vs Enoxaparin

Treatments

Studied treatment

apixaban 2.5 mg orally twice daily for 10 to 14 days
started 12 to 24 hours after surgery and continued for 10 to 14 days

Control treatment

enoxaparin 30mg subcutaneously every 12 hours
started 12 to 24 hours after surgery and continued for 10 to 14 days

Treatments description

enoxaprin regimen	started after surgery
treatment duration	10-14 days

Patients

patients undergoing knee-replacement surgery

Inclusion criteria

scheduled to undergo total knee replacement surgery for one or both knees, including revision of a previously inserted artificial joint

Exclusion criteria

active bleeding or a contraindication to anticoagulant prophylaxis; ongoing anticoagulant or antiplatelet treatment;uncontrolled hypertension, active hepatobiliary disease; clinically significant impairment of renal function, thrombocytopenia; anemia; allergy to heparin, and allergy to radiographic contrast dye or another contraindication to bilateral venography

Baseline characteristics

Age (mean), years	65.8y
Total hip replacement	0%
Total knee replacement	100%
Weight, kg,	86.7 kg
Female	62.1%
general anesthesia	43.2%

Method and design

Randomized effectives	1599 / 1596 (studied vs. control)
Design	Parallel groups
Blinding	double blind
Follow-up duration	10-14 days
Number of centre	129
Geographic area	14 countries
Hypothesis	Non inferiority
Primary endpoint	a- and symptomatic DVT, non fatal PE, death

Results

Endpoint Studied treat.
n/N Control treat.
n/N Graph RR [95% CI]

All cause death

3 / 1599
3 / 1596
classic 1,00 [0,20;4,94]

major or clinically relevant non-major bleeding

46 / 1596
68 / 1588
0,67 [0,47;0,97]

proximal DVT

9 / 1254
11 / 1207
0,79 [0,33;1,89]

Deep vein thrombosis

89 / 1142
92 / 1122
0,95 [0,72;1,26]

total VTE and all-cause mortality

104 / 1157
100 / 1130
1,02 [0,78;1,32]

Major bleeding

11 / 1596
22 / 1588
0,50 [0,24;1,02]

Symptomatic venous thromboembolism (DVT, PE)

19 / 1599
13 / 1596
classic 1,46 [0,72;2,94] 0 2 1.0

Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
Relative risks
Endpoint	Studied treat.	Control treat.	Relative Risk	95% CI	Endpoint definition in the trial	Ref
major or clinically relevant non-major bleeding	46 / 1596 (2,9%)	68 / 1588 (4,3%)	0,67	[0,47;0,97]		11133
All cause death	3 / 1599 (0,2%)	3 / 1596 (0,2%)	1,00	[0,20;4,94]	Intended treatment period	11133
proximal DVT	9 / 1254 (0,7%)	11 / 1207 (0,9%)	0,79	[0,33;1,89]		11133
Major bleeding	11 / 1596 (0,7%)	22 / 1588 (1,4%)	0,50	[0,24;1,02]	Adjudicated major bleeding events	11133
Symptomatic venous thromboembolism (DVT, PE)	19 / 1599 (1,2%)	13 / 1596 (0,8%)	1,46	[0,72;2,94]	Symptomatic VTE and VTE related death	11133
total VTE and all-cause mortality	104 / 1157 (9,0%)	100 / 1130 (8,8%)	1,02	[0,78;1,32]	Intended treatment period	11133
Deep vein thrombosis	89 / 1142 (7,8%)	92 / 1122 (8,2%)	0,95	[0,72;1,26]	all DVT	11133
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 11133: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJApixaban or enoxaparin for thromboprophylaxis after knee replacement.N Engl J Med 2009;361:594-604 0:

Endpoint	Events rate		Absolute risk reduction (ARR)
Absolute risk reduction
Endpoint	Studied treat.	Control treat.	Absolute risk reduction (ARR)
major or clinically relevant non-major bleeding	2,88%	4,28%	-14,0‰
All cause death	1,88‰	1,88‰	-0,0‰
proximal DVT	7,18‰	9,11‰	-1,9‰
Major bleeding	6,89‰	1,39%	-7,0‰
Symptomatic venous thromboembolism (DVT, PE)	1,19%	8,15‰	3,7‰
total VTE and all-cause mortality	8,99%	8,85%	1,4‰
Deep vein thrombosis	7,79%	8,20%	-4,1‰

Meta-analysis of all similar trials:

anticoagulant in DVT prophylaxis for orthopedic surgery

direct factor Xa inhibitors in DVT prophylaxis for all type of patients

new anticoagulants in DVT prophylaxis for all type of patients

new anticoagulants in DVT prophylaxis for elective major knee surgery

Reference(s)

Trials register #

NCT00371683

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;361:594-604
Pubmed | Hubmed | Fulltext

ADVANCE-1 study, 2008

Treatments

Patients

Method and design

Results

Reference(s)