Related trials
AMPLIFY, 2013 - apixaban (without LMWH) vs LMWH/VKA
Edoxaban Hokusai VTE, 2013 - heparin/edoxaban vs heparin/VKA
AMPLIFY-EXT 5mg, 2012 - apixaban 5mg vs discontinuation
AMPLIFY-EXT 2.5mg, 2012 - apixaban 2.5mg vs discontinuation
Einstein-PE Evaluation, 2012 - rivaroxaban (without LMWH) vs LMWH/VKA
RE-MEDY, 2011 - dabigatran vs warfarin
RE-COVER II, 2011 - heparin/dabigatran vs heparin/VKA
RE-SONATE, 2011 - dabigatran vs discontinuation
Einstein-DVT Evaluation, 2010 - rivaroxaban (without LMWH) vs LMWH/VKA
EINSTEIN-extension, 2009 - rivaroxaban vs discontinuation
RE-COVER, 2009 - heparin/dabigatran vs heparin/VKA
Einstein-DVT Dose-Ranging Study, 2008 - rivaroxaban (without LMWH) vs LMWH/VKA
Botticelli DVT, 2008 - apixaban (without LMWH) vs LMWH/VKA
VanGogh extension, 2007 - idraparinux vs discontinuation
THRIVE I, 2003 - ximelagatran (without LMWH) vs LMWH/VKA
THRIVE III, 2003 - ximelagatran vs discontinuation
See also:
All venous thrombosis clinical trials
All clinical trials of new oral anticoagulants
All clinical trials of heparin/edoxaban
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Treatments
Studied treatment |
heparin then edoxaban 60mg daily (30mg if creatine clearnce of 30 to 50 ml/min or <60kg) for 3 to 12 months
edoxaban at a dose of 60 mg once daily, or 30 mg once daily (e.g., in the case of
patients with creatinine clearance of 30 to 50 ml per minute or a body weight below
60 kg) after initial treatment with heparin of at least 5 days
|
Control treatment |
heparin then warfarin
|
Concomittant treatment |
initial treatment with heparin of at least 5 days |
Patients
Patients |
patients
with acute venous thromboembolism, who had initially received heparin, |
Method and design
Randomized effectives |
4143 / 4149 (studied vs. control) |
Design |
Parallel groups |
Blinding |
double-blind |
Hypothesis |
Non inferiority |
Primary endpoint |
recurrent symptomatic venous thromboembolism |
Results
Endpoints and data reported in the trial's publication(s)
Endpoint |
Events (%) |
Relative Risk |
95% CI |
|
Studied treat. |
Control treat. |
Event during overall study period |
130 / 4143 (3,1%) |
146 / 4149 (3,5%) |
0,89 |
[0,71;1,12] |
|
Fatal PE during study period |
4 / 4143 (0,1%) |
3 / 4149 (0,1%) |
1,34 |
[0,30;5,96] |
|
Death, with PE not ruled out during study period |
20 / 4143 (0,5%) |
21 / 4149 (0,5%) |
0,95 |
[0,52;1,76] |
|
Nonfatal PE with or without DVT during study period |
49 / 4143 (1,2%) |
59 / 4149 (1,4%) |
0,83 |
[0,57;1,21] |
|
DVT alone during study period |
57 / 4143 (1,4%) |
63 / 4149 (1,5%) |
0,91 |
[0,63;1,29] |
|
Event during on-treatment period |
66 / 4143 (1,6%) |
80 / 4149 (1,9%) |
0,83 |
[0,60;1,14] |
|
major or clinically relevant nonmajor bleeding |
349 / 4143 (8,4%) |
423 / 4149 (10,2%) |
0,83 |
[0,72;0,95] |
|
Major bleeding |
56 / 4143 (1,4%) |
66 / 4149 (1,6%) |
0,85 |
[0,60;1,21] |
|
Fatal bleeding |
2 / 4143 (0,0%) |
10 / 4149 (0,2%) |
0,20 |
[0,04;0,91] |
|
Intracranial Fatal bleeding |
0 / 4143 (0,0%) |
6 / 4149 (0,1%) |
0,08 |
[0,00;1,49] |
|
Gastrointestinal Fatal bleeding |
1 / 4143 (0,0%) |
2 / 4149 (0,0%) |
0,50 |
[0,05;5,52] |
|
Retroperitoneal Fatal bleeding |
0 / 4143 (0,0%) |
1 / 4149 (0,0%) |
0,50 |
[0,02;14,92] |
|
Other Fatal bleeding |
1 / 4143 (0,0%) |
1 / 4149 (0,0%) |
1,00 |
[0,06;16,01] |
|
Nonfatal major bleeding |
13 / 4143 (0,3%) |
25 / 4149 (0,6%) |
0,52 |
[0,27;1,02] |
|
Intracranial Nonfatal major bleeding |
5 / 4143 (0,1%) |
12 / 4149 (0,3%) |
0,42 |
[0,15;1,18] |
|
Retroperitoneal Nonfatal major bleeding |
0 / 4143 (0,0%) |
3 / 4149 (0,1%) |
0,17 |
[0,01;3,33] |
|
Other Nonfatal major bleeding |
8 / 4143 (0,2%) |
10 / 4149 (0,2%) |
0,80 |
[0,32;2,03] |
|
Nonfatal in noncritical site major bleeding |
41 / 4143 (1,0%) |
33 / 4149 (0,8%) |
1,24 |
[0,79;1,96] |
|
Clinically relevant nonmajor bleeding |
298 / 4143 (7,2%) |
368 / 4149 (8,9%) |
0,81 |
[0,70;0,94] |
|
Any bleeding |
895 / 4143 (21,6%) |
1056 / 4149 (25,5%) |
0,85 |
[0,79;0,92] |
|
Endpoints used by the meta-analysis and data retained for this trial
Endpoint
Studied treat. n/N
Control treat. n/N
Graph
RR [95% CI]
Bleeding
895 / 4143
1056 / 4149
0,85 [0,79;0,92]
fatal pulmonary embolism
4 / 4143
3 / 4149
classic
1,34 [0,30;5,96]
major or clinically relevant non-major bleeding
349 / 4143
423 / 4149
0,83 [0,72;0,95]
Major bleeding
56 / 4143
66 / 4149
0,85 [0,60;1,21]
recurrent VTE during treatment
66 / 4143
80 / 4149
0,83 [0,60;1,14]
non-fatal pulmonary embolism
49 / 4143
59 / 4149
0,83 [0,57;1,21]
0
2
1.0
Relative risks
|
Endpoint |
Events (%) |
Relative Risk |
95% CI |
Endpoint definition in the trial |
Ref |
Studied treat. |
Control treat. |
Major bleeding
|
56 / 4143 (1,4%) |
66 / 4149 (1,6%) |
0,85 |
[0,60;1,21] |
Major bleeding |
|
recurrent VTE during treatment
|
66 / 4143 (1,6%) |
80 / 4149 (1,9%) |
0,83 |
[0,60;1,14] |
Event during on-treatment period |
|
non-fatal pulmonary embolism
|
49 / 4143 (1,2%) |
59 / 4149 (1,4%) |
0,83 |
[0,57;1,21] |
Nonfatal PE with or without DVT during study period |
|
major or clinically relevant non-major bleeding
|
349 / 4143 (8,4%) |
423 / 4149 (10,2%) |
0,83 |
[0,72;0,95] |
major or clinically relevant nonmajor bleeding |
|
Bleeding
|
895 / 4143 (21,6%) |
1056 / 4149 (25,5%) |
0,85 |
[0,79;0,92] |
Any bleeding |
|
fatal pulmonary embolism
|
4 / 4143 (0,1%) |
3 / 4149 (0,1%) |
1,34 |
[0,30;5,96] |
Fatal PE during study period |
|
The primary endpoint (if exists) appears in blod characters
|
Reference(s) used for data extraction:
0:
|
Endpoint |
studied treat. |
control treat. |
mean diff |
Absolute risk reduction
|
Endpoint |
Events rate |
Absolute risk reduction (ARR) |
Studied treat. |
Control treat. |
Major bleeding |
1,35% |
1,59% |
-2,4‰
|
recurrent VTE during treatment |
1,59% |
1,93% |
-3,4‰
|
non-fatal pulmonary embolism |
1,18% |
1,42% |
-2,4‰
|
major or clinically relevant non-major bleeding |
8,42% |
10,20% |
-17,7‰
|
Bleeding |
21,60% |
25,45% |
-38,5‰
|
fatal pulmonary embolism |
0,97‰ |
0,72‰ |
0,2‰
|
Meta-analysis of all similar trials:
new oral anticoagulants in venous thrombosis for all types of patients
Reference(s)
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