RE-NOVATE (220mg) trial

any bleeding diathesis; history of acute intracranial disease or haemorrhagic stroke; major surgery, trauma, uncontrolled hypertension, or myocardial infarction in the past 3 months; gastrointestinal or urogenital bleeding, or ulcer disease in the past 6 months; severe liver disease; alanine or aspartate aminotransferase concentrations greater than two times the upper limit of the normal range in the past month; severe renal insuffi ciency (creatinine clearance less than 30 mL/min); use of long-acting non-steroidal anti-infl ammatory drugs

Baseline characteristics

Age (mean), years	64y
Total hip replacement	100%
Total knee replacement	0%
Weight, kg,	79 kg
Female	56%
general anesthesia	25%
BMI (kg/m�)	NA
History of venous thromboembolism (%)	3%
Use of cement	NA
Estimated creatinine clearance >60 ml/min	NA (mean 89 ml/min)
Previous orthopedic surgery (%)	NA
Duration of surgery (min)	86 min

Method and design

Randomized effectives	1157 / 1162 (studied vs. control)
Design	Parallel groups
Blinding	double blind
Follow-up duration	28-35 days, median 33d
Number of centre	115
Geographic area	Europe, Australia, South Africa
Primary endpoint	total VTE and all-cause mortality

Results

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

All cause death

3 / 1137
0 / 1142
classic 13,06 [0,22;762,41]

asymptomatic DVT

40 / 880
56 / 897
0,73 [0,49;1,08]

non-fatal pulmonary embolism

5 / 880
3 / 897
classic 1,70 [0,41;7,09]

proximal DVT

18 / 905
32 / 914
0,57 [0,32;1,00]

Major bleeding

23 / 1146
18 / 1154
classic 1,29 [0,70;2,37]

total VTE and all-cause mortality

53 / 880
60 / 897
0,90 [0,63;1,29]

Symptomatic deep-vein thrombosis

6 / 1137
1 / 1142
classic 6,03 [0,73;49,98]

distal DVT

22 / 874
24 / 894
0,94 [0,53;1,66]

major VTE (fatal and non fatal DVT,PE)

28 / 909
36 / 917
0,78 [0,48;1,27] 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
All cause death	3 / 1137 (0,3%)	0 / 1142 (0,0%)	6,03	[0,30;120,18]		7390
asymptomatic DVT	40 / 880 (4,5%)	56 / 897 (6,2%)	0,73	[0,49;1,08]
non-fatal pulmonary embolism	5 / 880 (0,6%)	3 / 897 (0,3%)	1,70	[0,41;7,09]
proximal DVT	18 / 905 (2,0%)	32 / 914 (3,5%)	0,57	[0,32;1,00]	asymptomatic
Major bleeding	23 / 1146 (2,0%)	18 / 1154 (1,6%)	1,29	[0,70;2,37]
total VTE and all-cause mortality	53 / 880 (6,0%)	60 / 897 (6,7%)	0,90	[0,63;1,29]	during treatment period
Symptomatic deep-vein thrombosis	6 / 1137 (0,5%)	1 / 1142 (0,1%)	6,03	[0,73;49,98]		7390
distal DVT	22 / 874 (2,5%)	24 / 894 (2,7%)	0,94	[0,53;1,66]	asymptomatic distal
major VTE (fatal and non fatal DVT,PE)	28 / 909 (3,1%)	36 / 917 (3,9%)	0,78	[0,48;1,27]
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 7390: Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, B�ller HRDabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial.Lancet 2007;370:949-56

Endpoint	Events rate		Absolute risk reduction (ARR)
Absolute risk reduction
Endpoint	Studied treat.	Control treat.	Absolute risk reduction (ARR)
asymptomatic DVT	4,55%	6,24%	-17,0‰
non-fatal pulmonary embolism	5,68‰	3,34‰	2,3‰
proximal DVT	1,99%	3,50%	-15,1‰
Major bleeding	2,01%	1,56%	4,5‰
total VTE and all-cause mortality	6,02%	6,69%	-6,7‰
Symptomatic deep-vein thrombosis	5,28‰	0,88‰	4,4‰
distal DVT	2,52%	2,68%	-1,7‰
major VTE (fatal and non fatal DVT,PE)	3,08%	3,93%	-8,5‰

Meta-analysis of all similar trials:

anticoagulant in DVT prophylaxis for orthopedic surgery

antithrombotics in DVT prophylaxis for elective hip replacement

antithrombotics in DVT prophylaxis for orthopedic surgery

direct antithrombins in DVT prophylaxis for all type of patients

new anticoagulants in DVT prophylaxis for elective hip replacement

new anticoagulants in DVT prophylaxis for orthopaedic surgery

new anticoagulants in DVT prophylaxis for all type of patients

Reference(s)

Trials register #

NCT00168818

Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, B�ller HR. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial.. Lancet 2007;370:949-56
Pubmed | Hubmed | Fulltext

RE-NOVATE (220mg) study, 2007

Treatments

Patients

Method and design

Results

Reference(s)