RE-COVER I: Efficacy and Safety of Dabigatran Compared to Warfarin for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT00291330
Collaborator
(none)
2,564
250
2
10.3
Study Details
Study Description
Brief Summary
The purpose of this trial is to determine the comparative safety and efficacy of dabigatran etexilate 150 mg bid administered orally and warfarin as needed (pro re nata - prn) to maintain an International Normalised Ratio (INR) of 2.0-3.0 for 6 month treatment of acute symptomatic venous thromboembolism (VTE), following initial treatment (5-10 days) with a parenteral anticoagulant approved for this indication. This trial aims to demonstrate non-inferiority of dabigatran compared with warfarin in patients with acute symptomatic VTE. After achieving non-inferiority, this trial also aims to establish superiority (by means of hierarchical tests) of dabigatran over warfarin.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
2564 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Primary Purpose:
Treatment
Official Title:
A Phase III, Randomised, Double Blind, Parallel-group Study of the Efficacy and Safety of Oral Dabigatran Etexilate 150 mg Twice Daily Compared to Warfarin (INR 2.0-3.0) for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism (VTE), Following Initial Treatment (5-10 Days) With a Parenteral Anticoagulant Approved for This Indication.
Study Start Date
:
Feb 1, 2006
Actual Primary Completion Date
:
May 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: dabigatran etexilate 150 mg twice daily |
Drug: dabigatran etexilate 150 mg
twice daily
|
| Active Comparator: warfarin (INR 2-3) prn to maintain INR (2-3) |
Drug: warfarin (INR 2-3)
prn to maintain INR (2-3)
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE [For statistical analysis 1: from randomisation to end of post treatment period (ptp), planned to be up to day 224. For statistical analysis 2: from randomisation to 6 months (up to day 180)]
All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
Secondary Outcome Measures
- Number of Participants With Recurrent Symptomatic VTE and All Deaths [For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224.]
VTE or any death which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
- Number of Participants With Recurrent Symptomatic DVT [For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224.]
Symptomatic DVT which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
- Number of Participants With Recurrent Symptomatic Non-fatal PE [For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224.]
Symptomatic non-fatal PE which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
- Number of Participants Who Died Due to VTE [For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224.]
VTE - related deaths which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
- Number of Participants Who Died (Any Cause) [For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224.]
Any deaths which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
- Number of Participants With Bleeding Events [From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug)]
Major bleeding events (MBE) were defined as Fatal bleeding Symptomatic bleeding in a critical area or organ Bleeding causing a fall in haemoglobin level of 20 g/L (1.24 mmol/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells Clinically-relevant bleeding events (CRBE) was defined as spontaneous skin hematoma >=25 cm² spontaneous nose bleed >5 min macroscopic hematuria spontaneous or >24 hours if associated with an intervention spontaneous rectal bleeding (more than spotting on toilet paper) gingival bleeding >5 min leading to hospitalisation and / or requiring surgical treatment leading to a transfusion of <2 units of whole blood or red cells any other bleeding event considered clinically relevant by the investigator Any bleeding events were defined as major, clinically-relevant and nuisance bleeding events. Nuisance bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.
- Number of Participants With Acute Coronary Syndrome (ACS) [From first intake of study drug to end of study conduct]
Any ACS occurring during the conduct of the study (centrally adjudicated as definite). Counts of patients having a centrally adjudicated definite ACS during intake of active study drug, after stopping active study drug and before or without intake of active study drug, according to treatment group. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
- Laboratory Analyses [From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug)]
Frequency of patients with possible clinically significant abnormalities.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria
-
Acute deep vein thrombosis (DVT) of the leg involving proximal veins, and/or pulmonary embolism (PE) iin patients for whom at least 6 months of anticoagulant therapy is considered appropriate
-
Male or female, being 18 years of age or older
-
Written informed consent for study participation
Exclusion criteria
-
Overt symptoms of VTE for longer than 2 weeks prior to enrolment
-
PE satisfying at least one of the following criteria: Haemodynamic instability, embolectomy is indicated or performed, thrombolytic therapy is indicated or performed, or suspected source of PE is other than the legs
-
Actual or anticipated use of vena cava filter
-
Contraindications to anticoagulant therapy
-
Patients who in the investigators opinion should not be treated with warfarin
-
Allergy to heparins or other alternate approved therapy used for initial treatment, warfarin or dabigatran, or to one of the excipients included in these medications
-
Patients who in the investigators judgement are perceived as having an excessive risk of bleeding
-
Known anaemia
-
Need of anticoagulant treatment for disorders other than VTE
-
Recent unstable cardiovascular disease
-
Elevated AST or ALT > 2x ULN
-
Liver disease expected to have any potential impact on survival
-
Patients who have developed transaminase elevations upon exposure to ximelagatran
-
Severe renal impairment
-
Women who are pregnant, nursing, or of childbearing potential who refuse to use a medically acceptable form of contraception
-
Participation in another clinical trial with an investigational drug during the last 30 days or previous participation in this study
-
Patients considered unsuitable for inclusion by the investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1160.53.01035 Boehringer Ingelheim Investigational Site | Mobile | Alabama | United States | |
| 2 | 1160.53.01056 Boehringer Ingelheim Investigational Site | Hartford | Connecticut | United States | |
| 3 | 1160.53.01044 Boehringer Ingelheim Investigational Site | Clearwater | Florida | United States | |
| 4 | 1160.53.01033 Boehringer Ingelheim Investigational Site | Sarasota | Florida | United States | |
| 5 | 1160.53.01046 Boehringer Ingelheim Investigational Site | Sarasota | Florida | United States | |
| 6 | 1160.53.01019 Boehringer Ingelheim Investigational Site | Augusta | Georgia | United States | |
| 7 | 1160.53.01008 Boehringer Ingelheim Investigational Site | Decatur | Georgia | United States | |
| 8 | 1160.53.01010 Boehringer Ingelheim Investigational Site | Marietta | Georgia | United States | |
| 9 | 1160.53.01014 Boehringer Ingelheim Investigational Site | Baltimore | Maryland | United States | |
| 10 | 1160.53.01023 Boehringer Ingelheim Investigational Site | Detroit | Michigan | United States | |
| 11 | 1160.53.01029 Boehringer Ingelheim Investigational Site | Pontiac | Michigan | United States | |
| 12 | 1160.53.01009 Boehringer Ingelheim Investigational Site | St. Louis Park | Minnesota | United States | |
| 13 | 1160.53.01031 Boehringer Ingelheim Investigational Site | Lebanon | New Hampshire | United States | |
| 14 | 1160.53.01036 Boehringer Ingelheim Investigational Site | Albuquerque | New Mexico | United States | |
| 15 | 1160.53.01025 Boehringer Ingelheim Investigational Site | Valhalla | New York | United States | |
| 16 | 1160.53.01027 Boehringer Ingelheim Investigational Site | Chapel Hill | North Carolina | United States | |
| 17 | 1160.53.01039 Boehringer Ingelheim Investigational Site | Winston-Salem | North Carolina | United States | |
| 18 | 1160.53.01030 Boehringer Ingelheim Investigational Site | Grand Forks | North Dakota | United States | |
| 19 | 1160.53.01013 Boehringer Ingelheim Investigational Site | Toledo | Ohio | United States | |
| 20 | 1160.53.01028 Boehringer Ingelheim Investigational Site | Portland | Oregon | United States | |
| 21 | 1160.53.01052 Boehringer Ingelheim Investigational Site | Altoona | Pennsylvania | United States | |
| 22 | 1160.53.01055 Boehringer Ingelheim Investigational Site | Summerville | South Carolina | United States | |
| 23 | 1160.53.01017 Boehringer Ingelheim Investigational Site | Richmond | Virginia | United States | |
| 24 | 1160.53.54017 Boehringer Ingelheim Investigational Site | Adrogué | Argentina | ||
| 25 | 1160.53.54003 Boehringer Ingelheim Investigational Site | Capital Federal | Argentina | ||
| 26 | 1160.53.54005 Boehringer Ingelheim Investigational Site | Capital Federal | Argentina | ||
| 27 | 1160.53.54006 Boehringer Ingelheim Investigational Site | Capital Federal | Argentina | ||
| 28 | 1160.53.54007 Boehringer Ingelheim Investigational Site | Capital Federal | Argentina | ||
| 29 | 1160.53.54010 Boehringer Ingelheim Investigational Site | Capital Federal | Argentina | ||
| 30 | 1160.53.61002 Boehringer Ingelheim Investigational Site | Woolloongabba | Queensland | Australia | |
| 31 | 1160.53.61004 Boehringer Ingelheim Investigational Site | Bedford Park | South Australia | Australia | |
| 32 | 1160.53.61003 Boehringer Ingelheim Investigational Site | Box Hill | Victoria | Australia | |
| 33 | 1160.53.61001 Boehringer Ingelheim Investigational Site | Clayton | Victoria | Australia | |
| 34 | 1160.53.61006 The Avenue Cardiovascular Centre | Windsor | Victoria | Australia | |
| 35 | 1160.53.61005 Boehringer Ingelheim Investigational Site | Perth | Western Australia | Australia | |
| 36 | 1160.53.43001 Boehringer Ingelheim Investigational Site | Graz | Austria | ||
| 37 | 1160.53.43003 Boehringer Ingelheim Investigational Site | Innsbruck | Austria | ||
| 38 | 1160.53.43002 Boehringer Ingelheim Investigational Site | Wien | Austria | ||
| 39 | 1160.53.32003 Boehringer Ingelheim Investigational Site | Brussel | Belgium | ||
| 40 | 1160.53.32001 Boehringer Ingelheim Investigational Site | Bruxelles | Belgium | ||
| 41 | 1160.53.32002 Boehringer Ingelheim Investigational Site | Bruxelles | Belgium | ||
| 42 | 1160.53.32007 Boehringer Ingelheim Investigational Site | Edegem | Belgium | ||
| 43 | 1160.53.32005 Boehringer Ingelheim Investigational Site | Leuven | Belgium | ||
| 44 | 1160.53.32004 Boehringer Ingelheim Investigational Site | Liège | Belgium | ||
| 45 | 1160.53.55010 Boehringer Ingelheim Investigational Site | Brasília | Brazil | ||
| 46 | 1160.53.55007 Boehringer Ingelheim Investigational Site | Campinas | Brazil | ||
| 47 | 1160.53.55001 Boehringer Ingelheim Investigational Site | Cerqueira César - Sao Paulo | Brazil | ||
| 48 | 1160.53.55002 Boehringer Ingelheim Investigational Site | Cerqueira César - São Paulo | Brazil | ||
| 49 | 1160.53.55014 Boehringer Ingelheim Investigational Site | Cristo Rei - Curitiba | Brazil | ||
| 50 | 1160.53.55011 Boehringer Ingelheim Investigational Site | Goiânia - | Brazil | ||
| 51 | 1160.53.55017 Boehringer Ingelheim Investigational Site | Paraná - | Brazil | ||
| 52 | 1160.53.55012 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil | ||
| 53 | 1160.53.55016 Boehringer Ingelheim Investigational Site | Rio de Janeiro - RJ | Brazil | ||
| 54 | 1160.53.55004 Boehringer Ingelheim Investigational Site | Santo André | Brazil | ||
| 55 | 1160.53.55005 Boehringer Ingelheim Investigational Site | São José do Rio Preto | Brazil | ||
| 56 | 1160.53.02006 Boehringer Ingelheim Investigational Site | Edmonton | Alberta | Canada | |
| 57 | 1160.53.02013 Boehringer Ingelheim Investigational Site | Edmonton | Alberta | Canada | |
| 58 | 1160.53.02021 Boehringer Ingelheim Investigational Site | Victoria | British Columbia | Canada | |
| 59 | 1160.53.02004 Boehringer Ingelheim Investigational Site | Saint Johns | New Brunswick | Canada | |
| 60 | 1160.53.02001 Boehringer Ingelheim Investigational Site | Halifax | Nova Scotia | Canada | |
| 61 | 1160.53.02002 Boehringer Ingelheim Investigational Site | Hamilton | Ontario | Canada | |
| 62 | 1160.53.02005 Boehringer Ingelheim Investigational Site | Hamilton | Ontario | Canada | |
| 63 | 1160.53.02010 Boehringer Ingelheim Investigational Site | Hamilton | Ontario | Canada | |
| 64 | 1160.53.02022 Boehringer Ingelheim Investigational Site | Hamilton | Ontario | Canada | |
| 65 | 1160.53.02011 Boehringer Ingelheim Investigational Site | London | Ontario | Canada | |
| 66 | 1160.53.02015 Boehringer Ingelheim Investigational Site | Ottawa | Ontario | Canada | |
| 67 | 1160.53.02019 Boehringer Ingelheim Investigational Site | Toronto | Ontario | Canada | |
| 68 | 1160.53.02008 Boehringer Ingelheim Investigational Site | Montreal | Quebec | Canada | |
| 69 | 1160.53.02009 Boehringer Ingelheim Investigational Site | Montreal | Quebec | Canada | |
| 70 | 1160.53.02014 Boehringer Ingelheim Investigational Site | Montreal | Quebec | Canada | |
| 71 | 1160.53.02017 Boehringer Ingelheim Investigational Site | Montreal | Quebec | Canada | |
| 72 | 1160.53.02003 Boehringer Ingelheim Investigational Site | Sainte-Foy | Quebec | Canada | |
| 73 | 1160.53.02020 Boehringer Ingelheim Investigational Site | Quebec | Canada | ||
| 74 | 1160.53.42001 Boehringer Ingelheim Investigational Site | Brno | Czech Republic | ||
| 75 | 1160.53.42002 Boehringer Ingelheim Investigational Site | Hradec Kralove | Czech Republic | ||
| 76 | 1160.53.42011 Boehringer Ingelheim Investigational Site | Hranice | Czech Republic | ||
| 77 | 1160.53.42009 Boehringer Ingelheim Investigational Site | Jihlava | Czech Republic | ||
| 78 | 1160.53.42012 Boehringer Ingelheim Investigational Site | Liberec | Czech Republic | ||
| 79 | 1160.53.42015 Boehringer Ingelheim Investigational Site | Novy Jicin | Czech Republic | ||
| 80 | 1160.53.42005 Boehringer Ingelheim Investigational Site | Ostrava-Vitkovice | Czech Republic | ||
| 81 | 1160.53.42004 Boehringer Ingelheim Investigational Site | Praha 2 | Czech Republic | ||
| 82 | 1160.53.42014 Boehringer Ingelheim Investigational Site | Tabor | Czech Republic | ||
| 83 | 1160.53.42016 Boehringer Ingelheim Investigational Site | Teplice | Czech Republic | ||
| 84 | 1160.53.42010 Boehringer Ingelheim Investigational Site | Usti nad Labem | Czech Republic | ||
| 85 | 1160.53.42007 Boehringer Ingelheim Investigational Site | Zlin | Czech Republic | ||
| 86 | 1160.53.45008 Boehringer Ingelheim Investigational Site | Esbjerg | Denmark | ||
| 87 | 1160.53.45009 Boehringer Ingelheim Investigational Site | Holbæk | Denmark | ||
| 88 | 1160.53.45002 Boehringer Ingelheim Investigational Site | Kolding | Denmark | ||
| 89 | 1160.53.45004 Boehringer Ingelheim Investigational Site | København NV | Denmark | ||
| 90 | 1160.53.45007 Boehringer Ingelheim Investigational Site | København S | Denmark | ||
| 91 | 1160.53.45006 Boehringer Ingelheim Investigational Site | Slagelse | Denmark | ||
| 92 | 1160.53.3301A Boehringer Ingelheim Investigational Site | Brest Cedex | France | ||
| 93 | 1160.53.3301B Boehringer Ingelheim Investigational Site | Brest Cedex | France | ||
| 94 | 1160.53.3301C Boehringer Ingelheim Investigational Site | Brest Cedex | France | ||
| 95 | 1160.53.3301D Boehringer Ingelheim Investigational Site | Brest Cedex | France | ||
| 96 | 1160.53.3301E Boehringer Ingelheim Investigational Site | Brest Cedex | France | ||
| 97 | 1160.53.3301F Boehringer Ingelheim Investigational Site | Brest Cedex | France | ||
| 98 | 1160.53.3301H Boehringer Ingelheim Investigational Site | Brest Cedex | France | ||
| 99 | 1160.53.3301I Boehringer Ingelheim Investigational Site | Brest Cedex | France | ||
| 100 | 1160.53.3302A Boehringer Ingelheim Investigational Site | Lorient | France | ||
| 101 | 1160.53.3310A Boehringer Ingelheim Investigational Site | Montpellier Cedex 5 | France | ||
| 102 | 1160.53.3310B Boehringer Ingelheim Investigational Site | Montpellier Cedex 5 | France | ||
| 103 | 1160.53.3310C Boehringer Ingelheim Investigational Site | Montpellier Cedex 5 | France | ||
| 104 | 1160.53.3308B Boehringer Ingelheim Investigational Site | Nancy | France | ||
| 105 | 1160.53.3303B Boehringer Ingelheim Investigational Site | St Etienne Cedex 2 | France | ||
| 106 | 1160.53.3303C Boehringer Ingelheim Investigational Site | St Etienne Cedex 2 | France | ||
| 107 | 1160.53.3303D Boehringer Ingelheim Investigational Site | St Etienne Cedex 2 | France | ||
| 108 | 1160.53.3303E Boehringer Ingelheim Investigational Site | St Etienne Cedex 2 | France | ||
| 109 | 1160.53.3303A Boehringer Ingelheim Investigational Site | St Priest en Jarez | France | ||
| 110 | 1160.53.3311A Boehringer Ingelheim Investigational Site | Toulon Naval | France | ||
| 111 | 1160.53.3311B Boehringer Ingelheim Investigational Site | Toulon Naval | France | ||
| 112 | 1160.53.3311C Boehringer Ingelheim Investigational Site | Toulon Naval | France | ||
| 113 | 1160.53.3311D Boehringer Ingelheim Investigational Site | Toulon Naval | France | ||
| 114 | 1160.53.3311E Boehringer Ingelheim Investigational Site | Toulon Naval | France | ||
| 115 | 1160.53.3308A Boehringer Ingelheim Investigational Site | Vandoeuvre les Nancy | France | ||
| 116 | 1160.53.49017 Boehringer Ingelheim Investigational Site | Dresden | Germany | ||
| 117 | 1160.53.49018 Boehringer Ingelheim Investigational Site | Dresden | Germany | ||
| 118 | 1160.53.49003 Boehringer Ingelheim Investigational Site | Köln | Germany | ||
| 119 | 1160.53.49005 Boehringer Ingelheim Investigational Site | Mannheim | Germany | ||
| 120 | 1160.53.49007 Boehringer Ingelheim Investigational Site | München | Germany | ||
| 121 | 1160.53.49009 Boehringer Ingelheim Investigational Site | Püttlingen | Germany | ||
| 122 | 1160.53.30001 Boehringer Ingelheim Investigational Site | Athens | Greece | ||
| 123 | 1160.53.30005 Boehringer Ingelheim Investigational Site | Athens | Greece | ||
| 124 | 1160.53.30006 Boehringer Ingelheim Investigational Site | Athens | Greece | ||
| 125 | 1160.53.36001 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 126 | 1160.53.36006 Boehringer Ingelheim Investigational Site | Budapest | Hungary | ||
| 127 | 1160.53.36002 Boehringer Ingelheim Investigational Site | Debrecen | Hungary | ||
| 128 | 1160.53.36013 Boehringer Ingelheim Investigational Site | Eger | Hungary | ||
| 129 | 1160.53.36012 Boehringer Ingelheim Investigational Site | Gyula | Hungary | ||
| 130 | 1160.53.36004 Boehringer Ingelheim Investigational Site | Miskolc | Hungary | ||
| 131 | 1160.53.36003 Boehringer Ingelheim Investigational Site | Pecs | Hungary | ||
| 132 | 1160.53.36011 Boehringer Ingelheim Investigational Site | Szombathely | Hungary | ||
| 133 | 1160.53.36010 Boehringer Ingelheim Investigational Site | Székesfehérvár | Hungary | ||
| 134 | 1160.53.91011 Boehringer Ingelheim Investigational Site | Bangalore | India | ||
| 135 | 1160.53.91012 Boehringer Ingelheim Investigational Site | Chennai | India | ||
| 136 | 1160.53.91019 Boehringer Ingelheim Investigational Site | Chennai | India | ||
| 137 | 1160.53.91013 Boehringer Ingelheim Investigational Site | Indore | India | ||
| 138 | 1160.53.91021 Boehringer Ingelheim Investigational Site | Karna | India | ||
| 139 | 1160.53.91022 Boehringer Ingelheim Investigational Site | Kerala | India | ||
| 140 | 1160.53.91020 Boehringer Ingelheim Investigational Site | Ludhiana | India | ||
| 141 | 1160.53.91007 Boehringer Ingelheim Investigational Site | Mysore | India | ||
| 142 | 1160.53.91015 Boehringer Ingelheim Investigational Site | Nagpur | India | ||
| 143 | 1160.53.91010 Boehringer Ingelheim Investigational Site | New Delhi | India | ||
| 144 | 1160.53.91005 Boehringer Ingelheim Investigational Site | Pune | India | ||
| 145 | 1160.53.91008 Boehringer Ingelheim Investigational Site | Pune | India | ||
| 146 | 1160.53.91004 Boehringer Ingelheim Investigational Site | Vadodara | India | ||
| 147 | 1160.53.97202 Boehringer Ingelheim Investigational Site | Afula | Israel | ||
| 148 | 1160.53.97207 Boehringer Ingelheim Investigational Site | Ashkelon | Israel | ||
| 149 | 1160.53.97211 Boehringer Ingelheim Investigational Site | Haifa | Israel | ||
| 150 | 1160.53.97203 Boehringer Ingelheim Investigational Site | Holon | Israel | ||
| 151 | 1160.53.97205 Boehringer Ingelheim Investigational Site | KfarSaba | Israel | ||
| 152 | 1160.53.97206 Boehringer Ingelheim Investigational Site | Petah Tiqwa | Israel | ||
| 153 | 1160.53.97204 Boehringer Ingelheim Investigational Site | Tel Hashomer | Israel | ||
| 154 | 1160.53.97210 Boehringer Ingelheim Investigational Site | Tel-Aviv | Israel | ||
| 155 | 1160.53.97201 Boehringer Ingelheim Investigational Site | Zerifin | Israel | ||
| 156 | 1160.53.39003 Boehringer Ingelheim Investigational Site | Bologna | Italy | ||
| 157 | 1160.53.39002 Boehringer Ingelheim Investigational Site | Padova | Italy | ||
| 158 | 1160.53.39001 Boehringer Ingelheim Investigational Site | Perugia | Italy | ||
| 159 | 1160.53.39004 Boehringer Ingelheim Investigational Site | Reggio Emilia | Italy | ||
| 160 | 1160.53.39007 Boehringer Ingelheim Investigational Site | Vimercate | Italy | ||
| 161 | 1160.53.39005 Boehringer Ingelheim Investigational Site | Vittorio Veneto (tv) | Italy | ||
| 162 | 1160.53.5264 Boehringer Ingelheim Investigational Site | Chihuahua | Mexico | ||
| 163 | 1160.53.5270 Boehringer Ingelheim Investigational Site | Culiacan | Mexico | ||
| 164 | 1160.53.5262 Boehringer Ingelheim Investigational Site | San Luis Potosí | Mexico | ||
| 165 | 1160.53.31010 Boehringer Ingelheim Investigational Site | 's Hertogenbosch | Netherlands | ||
| 166 | 1160.53.31001 Boehringer Ingelheim Investigational Site | Amersfoort | Netherlands | ||
| 167 | 1160.53.31006 Boehringer Ingelheim Investigational Site | Amsterdam | Netherlands | ||
| 168 | 1160.53.31013 Boehringer Ingelheim Investigational Site | Eindhoven | Netherlands | ||
| 169 | 1160.53.31005 Boehringer Ingelheim Investigational Site | Maastricht | Netherlands | ||
| 170 | 1160.53.31002 Boehringer Ingelheim Investigational Site | Nieuwegein | Netherlands | ||
| 171 | 1160.53.31004 Boehringer Ingelheim Investigational Site | Rotterdam | Netherlands | ||
| 172 | 1160.53.31009 Boehringer Ingelheim Investigational Site | Rotterdam | Netherlands | ||
| 173 | 1160.53.64003 Boehringer Ingelheim Investigational Site | Auckland | New Zealand | ||
| 174 | 1160.53.64004 Boehringer Ingelheim Investigational Site | Christchurch | New Zealand | ||
| 175 | 1160.53.64002 Boehringer Ingelheim Investigational Site | Otahuhu Auckland | New Zealand | ||
| 176 | 1160.53.64001 Boehringer Ingelheim Investigational Site | Takapuna Auckland | New Zealand | ||
| 177 | 1160.53.47001 Boehringer Ingelheim Investigational Site | Oslo | Norway | ||
| 178 | 1160.53.47004 Boehringer Ingelheim Investigational Site | Oslo | Norway | ||
| 179 | 1160.53.47003 Boehringer Ingelheim Investigational Site | Rud | Norway | ||
| 180 | 1160.53.47005 Boehringer Ingelheim Investigational Site | Trondheim | Norway | ||
| 181 | 1160.53.35104 Boehringer Ingelheim Investigational Site | Almada | Portugal | ||
| 182 | 1160.53.35109 Boehringer Ingelheim Investigational Site | Coimbra | Portugal | ||
| 183 | 1160.53.35101 Boehringer Ingelheim Investigational Site | Lisboa | Portugal | ||
| 184 | 1160.53.35102 Boehringer Ingelheim Investigational Site | Lisboa | Portugal | ||
| 185 | 1160.53.35105 Boehringer Ingelheim Investigational Site | Lisboa | Portugal | ||
| 186 | 1160.53.07011 Boehringer Ingelheim Investigational Site | Chelyabinsk | Russian Federation | ||
| 187 | 1160.53.07021 Boehringer Ingelheim Investigational Site | Chelyabinsk | Russian Federation | ||
| 188 | 1160.53.07007 Boehringer Ingelheim Investigational Site | Ekaterinburg | Russian Federation | ||
| 189 | 1160.53.07016 Boehringer Ingelheim Investigational Site | Krasnodar | Russian Federation | ||
| 190 | 1160.53.07004 Boehringer Ingelheim Investigational Site | Kursk | Russian Federation | ||
| 191 | 1160.53.07003 Boehringer Ingelheim Investigational Site | Moscow | Russian Federation | ||
| 192 | 1160.53.07010 Boehringer Ingelheim Investigational Site | Novosibirsk | Russian Federation | ||
| 193 | 1160.53.07020 Boehringer Ingelheim Investigational Site | Omsk | Russian Federation | ||
| 194 | 1160.53.07018 Boehringer Ingelheim Investigational Site | Pskov | Russian Federation | ||
| 195 | 1160.53.07009 Boehringer Ingelheim Investigational Site | Rostov-na-Donu | Russian Federation | ||
| 196 | 1160.53.07023 Boehringer Ingelheim Investigational Site | Rostov-na-Donu | Russian Federation | ||
| 197 | 1160.53.07024 Boehringer Ingelheim Investigational Site | Rostov-na-Donu | Russian Federation | ||
| 198 | 1160.53.07025 Boehringer Ingelheim Investigational Site | Rostov-na-Donu | Russian Federation | ||
| 199 | 1160.53.07001 Boehringer Ingelheim Investigational Site | St. Petersburg | Russian Federation | ||
| 200 | 1160.53.07014 Boehringer Ingelheim Investigational Site | Ufa | Russian Federation | ||
| 201 | 1160.53.07005 Boehringer Ingelheim Investigational Site | Yaroslavl | Russian Federation | ||
| 202 | 1160.53.07006 Boehringer Ingelheim Investigational Site | Yaroslavl | Russian Federation | ||
| 203 | 1160.53.42107 Boehringer Ingelheim Investigational Site | Banska Bystrica | Slovakia | ||
| 204 | 1160.53.42106 Boehringer Ingelheim Investigational Site | Lucenec | Slovakia | ||
| 205 | 1160.53.42102 Boehringer Ingelheim Investigational Site | Nitra | Slovakia | ||
| 206 | 1160.53.42103 Boehringer Ingelheim Investigational Site | Nove Zamky | Slovakia | ||
| 207 | 1160.53.42104 Boehringer Ingelheim Investigational Site | Zilina | Slovakia | ||
| 208 | 1160.53.27007 Boehringer Ingelheim Investigational Site | Centurion | South Africa | ||
| 209 | 1160.53.27001 Boehringer Ingelheim Investigational Site | Johannesburg | South Africa | ||
| 210 | 1160.53.27002 Boehringer Ingelheim Investigational Site | Johannesburg | South Africa | ||
| 211 | 1160.53.27004 Boehringer Ingelheim Investigational Site | Johannesburg | South Africa | ||
| 212 | 1160.53.27006 Boehringer Ingelheim Investigational Site | Johannesburg | South Africa | ||
| 213 | 1160.53.27009 Suite 404, Medical Centre | Pretoria | South Africa | ||
| 214 | 1160.53.27003 Boehringer Ingelheim Investigational Site | Randburg | South Africa | ||
| 215 | 1160.53.27008 Suite M5, Second Floor | Richards Bay | South Africa | ||
| 216 | 1160.53.27005 Boehringer Ingelheim Investigational Site | Roodepoort | South Africa | ||
| 217 | 1160.53.34012 Boehringer Ingelheim Investigational Site | Badalona (Barcelona) | Spain | ||
| 218 | 1160.53.34001 Boehringer Ingelheim Investigational Site | Barcelona | Spain | ||
| 219 | 1160.53.34002 Boehringer Ingelheim Investigational Site | Barcelona | Spain | ||
| 220 | 1160.53.34007 Boehringer Ingelheim Investigational Site | Cartagena. Murcia | Spain | ||
| 221 | 1160.53.34003 Boehringer Ingelheim Investigational Site | Cuenca | Spain | ||
| 222 | 1160.53.34009 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 223 | 1160.53.34010 Boehringer Ingelheim Investigational Site | Madrid | Spain | ||
| 224 | 1160.53.34004 Boehringer Ingelheim Investigational Site | Santander | Spain | ||
| 225 | 1160.53.34005 Boehringer Ingelheim Investigational Site | Torrelavega.Santander | Spain | ||
| 226 | 1160.53.34011 Boehringer Ingelheim Investigational Site | Valencia | Spain | ||
| 227 | 1160.53.46002 Boehringer Ingelheim Investigational Site | Göteborg | Sweden | ||
| 228 | 1160.53.46006 Boehringer Ingelheim Investigational Site | Jönköping | Sweden | ||
| 229 | 1160.53.46001 Boehringer Ingelheim Investigational Site | Stockholm | Sweden | ||
| 230 | 1160.53.46007 Boehringer Ingelheim Investigational Site | Stockholm | Sweden | ||
| 231 | 1160.53.46008 Boehringer Ingelheim Investigational Site | Stockholm | Sweden | ||
| 232 | 1160.53.46005 Boehringer Ingelheim Investigational Site | Sundsvall | Sweden | ||
| 233 | 1160.53.46003 Boehringer Ingelheim Investigational Site | Uppsala | Sweden | ||
| 234 | 1160.53.90003 Boehringer Ingelheim Investigational Site | Ankara | Turkey | ||
| 235 | 1160.53.90004 Boehringer Ingelheim Investigational Site | Ankara | Turkey | ||
| 236 | 1160.53.90005 Boehringer Ingelheim Investigational Site | Ankara | Turkey | ||
| 237 | 1160.53.90001 Boehringer Ingelheim Investigational Site | Istanbul | Turkey | ||
| 238 | 1160.53.90002 Boehringer Ingelheim Investigational Site | Istanbul | Turkey | ||
| 239 | 1160.53.90007 Boehringer Ingelheim Investigational Site | Istanbul | Turkey | ||
| 240 | 1160.53.90006 Boehringer Ingelheim Investigational Site | Izmir | Turkey | ||
| 241 | 1160.53.38006 Boehringer Ingelheim Investigational Site | Kiev | Ukraine | ||
| 242 | 1160.53.38005 Boehringer Ingelheim Investigational Site | Vinnitsa | Ukraine | ||
| 243 | 1160.53.38003 Boehringer Ingelheim Investigational Site | Zaporozhye | Ukraine | ||
| 244 | 1160.53.44008 Boehringer Ingelheim Investigational Site | Aberdeen | United Kingdom | ||
| 245 | 1160.53.44005 Boehringer Ingelheim Investigational Site | Headington, Oxford | United Kingdom | ||
| 246 | 1160.53.44004 Boehringer Ingelheim Investigational Site | London | United Kingdom | ||
| 247 | 1160.53.44009 Boehringer Ingelheim Investigational Site | London | United Kingdom | ||
| 248 | 1160.53.44011 Boehringer Ingelheim Investigational Site | London | United Kingdom | ||
| 249 | 1160.53.44006 Boehringer Ingelheim Investigational Site | Newcastle upon Tyne | United Kingdom | ||
| 250 | 1160.53.44012 Boehringer Ingelheim Investigational Site | Sheffield | United Kingdom |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00291330
Other Study ID Numbers:
- 1160.53
- 2005-001999-12
First Posted:
Feb 14, 2006
Last Update Posted:
Jun 6, 2014
Last Verified:
Apr 1, 2014
Study Results
Participant Flow
| Recruitment Details | There were 2564 patients enrolled/randomised in this trial but only 2539 started treatment |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Period Title: Overall Study | ||
| STARTED | 1273 | 1266 |
| COMPLETED | 1172 | 1169 |
| NOT COMPLETED | 101 | 97 |
Baseline Characteristics
| Arm/Group Title | Dabigatran 150 mg | Warfarin | Total |
|---|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 | Total of all reporting groups |
| Overall Participants | 1273 | 1266 | 2539 |
| Age (Year) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Year] |
55.0
(15.8)
|
54.4
(16.2)
|
54.7
(16.0)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
535
42%
|
520
41.1%
|
1055
41.6%
|
| Male |
738
58%
|
746
58.9%
|
1484
58.4%
|
| Acute symptomatic DVT of the leg and/or PE as assessed by investigator (participants) [Number] | |||
| Symptomatic PE and symptomatic DVT |
121
9.5%
|
124
9.8%
|
245
9.6%
|
| Symptomatic PE |
270
21.2%
|
271
21.4%
|
541
21.3%
|
| Symptomatic DVT |
880
69.1%
|
869
68.6%
|
1749
68.9%
|
| No PE and no DVT |
2
0.2%
|
2
0.2%
|
4
0.2%
|
Outcome Measures
| Title | Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE |
|---|---|
| Description | All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee. |
| Time Frame | For statistical analysis 1: from randomisation to end of post treatment period (ptp), planned to be up to day 224. For statistical analysis 2: from randomisation to 6 months (up to day 180) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken. |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Measure Participants | 1274 | 1265 |
| Participants with event (up to day 180) |
30
2.4%
|
27
2.1%
|
| Participants with event (up to end of ptp) |
34
2.7%
|
32
2.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the primary endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Non inferiority margin was set up to 2.75 for the HR analysis | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Non-inferiority P-Value. Two Statistical analyses performed on primary endpoint. Both non inferiority for the risk difference and for the hazard ratio analyses to be reached in order to conclude positively on the primary endpoint. | |
| Method | Regression, Cox | |
| Comments | Patients without events are censored at the end of post treatment period (day 224) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.05 | |
| Confidence Interval |
() 95% 0.65 to 1.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Risk difference vs. Warfarin for Proportion of patients with VTE or death related to VTE at 6 months. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Non inferiority margin was set up to 3.6% for the risk difference based on KM estimates | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Non-inferiority P-Value. Two Statistical analyses performed on primary endpoint. Both non inferiority for the risk difference and for the hazard ratio analyses to be reached in order to conclude positively on the primary endpoint. | |
| Method | Kaplan Meier weighted estimates | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (Percentage) |
| Estimated Value | 0.40 | |
| Confidence Interval |
() 95% -0.80 to 1.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Hazard ratio vs. Warfarin (events occurring between randomisation and the day 180). The time to first occurrence of the primary endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.10 | |
| Confidence Interval |
() 95% 0.65 to 1.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Recurrent Symptomatic VTE and All Deaths |
|---|---|
| Description | VTE or any death which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee. |
| Time Frame | For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken. |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Measure Participants | 1274 | 1265 |
| Participants with event (up to day 180) |
48
3.8%
|
44
3.5%
|
| Participants with event (up to end of ptp) |
55
4.3%
|
53
4.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Risk difference vs. Warfarin for Proportion of patients with VTE or death at 6 months. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6220 |
| Comments | ||
| Method | Kaplan Meier weighted estimates | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (Percentage) |
| Estimated Value | 0.30 | |
| Confidence Interval |
() 95% -1.00 to 1.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9844 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Patients without events are censored at the end of post treatment period (day 224) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.00 | |
| Confidence Interval |
() 95% 0.69 to 1.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Recurrent Symptomatic DVT |
|---|---|
| Description | Symptomatic DVT which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee. |
| Time Frame | For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken. |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Measure Participants | 1274 | 1265 |
| Participants with event (up to day 180) |
16
1.3%
|
18
1.4%
|
| Participants with event (up to end of ptp) |
17
1.3%
|
22
1.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Risk difference vs. Warfarin for Proportion of patients with symptomatic DVT at 6 months. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6466 |
| Comments | ||
| Method | Kaplan Meier weighted estimates | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (Percentage) |
| Estimated Value | -0.20 | |
| Confidence Interval |
() 95% -1.10 to 0.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3850 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Patients without events are censored at the end of post treatment period (day 224) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.76 | |
| Confidence Interval |
() 95% 0.40 to 1.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Recurrent Symptomatic Non-fatal PE |
|---|---|
| Description | Symptomatic non-fatal PE which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee. |
| Time Frame | For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken. |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Measure Participants | 1274 | 1265 |
| Participants with event (up to day 180) |
13
1%
|
7
0.6%
|
| Participants with event (up to end of ptp) |
16
1.3%
|
8
0.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Risk difference vs. Warfarin for Proportion of patients with symptomatic non-fatal PE at 6 months. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2981 |
| Comments | ||
| Method | Kaplan Meier weighted estimates | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (Percentage) |
| Estimated Value | 0.30 | |
| Confidence Interval |
() 95% -0.30 to 1.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1092 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Patients without events are censored at the end of post treatment period (day 224) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.00 | |
| Confidence Interval |
() 95% 0.86 to 4.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Who Died Due to VTE |
|---|---|
| Description | VTE - related deaths which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee. |
| Time Frame | For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken. |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Measure Participants | 1274 | 1265 |
| Participants with event (up to day 180) |
1
0.1%
|
3
0.2%
|
| Participants with event (up to end of ptp) |
1
0.1%
|
3
0.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Risk difference at 6 months vs. Warfarin for Proportion of patients who died due to VTE . Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5327 |
| Comments | ||
| Method | Kaplan Meier weighted estimates | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (Percentage) |
| Estimated Value | -0.30 | |
| Confidence Interval |
() 95% -1.20 to 0.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3332 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Patients without events are censored at the end of post treatment period (day 224) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.33 | |
| Confidence Interval |
() 95% 0.03 to 3.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Who Died (Any Cause) |
|---|---|
| Description | Any deaths which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee. |
| Time Frame | For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken. |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Measure Participants | 1274 | 1265 |
| Participants with event (up to day 180) |
21
1.6%
|
21
1.7%
|
| Participants with event (up to end of ptp) |
25
2%
|
25
2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Risk difference at 6 months vs. Warfarin for Proportion of patients who died from any cause. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8018 |
| Comments | ||
| Method | Kaplan Meier weighted estimates | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (Percentage) |
| Estimated Value | -0.10 | |
| Confidence Interval |
() 95% -1.00 to 0.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8203 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | Patients without events are censored at the end of post treatment period (day 224) | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.94 | |
| Confidence Interval |
() 95% 0.54 to 1.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Bleeding Events |
|---|---|
| Description | Major bleeding events (MBE) were defined as Fatal bleeding Symptomatic bleeding in a critical area or organ Bleeding causing a fall in haemoglobin level of 20 g/L (1.24 mmol/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells Clinically-relevant bleeding events (CRBE) was defined as spontaneous skin hematoma >=25 cm² spontaneous nose bleed >5 min macroscopic hematuria spontaneous or >24 hours if associated with an intervention spontaneous rectal bleeding (more than spotting on toilet paper) gingival bleeding >5 min leading to hospitalisation and / or requiring surgical treatment leading to a transfusion of <2 units of whole blood or red cells any other bleeding event considered clinically relevant by the investigator Any bleeding events were defined as major, clinically-relevant and nuisance bleeding events. Nuisance bleeding events were defined as all other bleeding events that did not fulfil the criteria from above. |
| Time Frame | From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set (TS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as treated. |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Measure Participants | 1273 | 1266 |
| Major bleeding events |
20
1.6%
|
24
1.9%
|
| MBE and/or CRBE |
71
5.6%
|
111
8.8%
|
| Any bleeding events |
207
16.3%
|
280
22.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Hazard ratio vs. Warfarin for the category major bleeding events (events occurring between 1st intake of study drug and last intake of study drug + 6 days). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5063 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.82 | |
| Confidence Interval |
() 95% 0.45 to 1.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Dabigatran 150 mg, Warfarin |
|---|---|---|
| Comments | Hazard ratio vs. Warfarin for the category of any bleeding events (events occurring between 1st intake of study drug and last intake of study drug + 6 days). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.71 | |
| Confidence Interval |
(2-Sided) 95% 0.59 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Acute Coronary Syndrome (ACS) |
|---|---|
| Description | Any ACS occurring during the conduct of the study (centrally adjudicated as definite). Counts of patients having a centrally adjudicated definite ACS during intake of active study drug, after stopping active study drug and before or without intake of active study drug, according to treatment group. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee. |
| Time Frame | From first intake of study drug to end of study conduct |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set (TS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as treated. |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Measure Participants | 1273 | 1266 |
| During intake of active study drug |
5
0.4%
|
3
0.2%
|
| After stopping active study drug |
4
0.3%
|
2
0.2%
|
| Before/without intake of active study drug |
2
0.2%
|
0
0%
|
| Title | Laboratory Analyses |
|---|---|
| Description | Frequency of patients with possible clinically significant abnormalities. |
| Time Frame | From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set (TS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as treated. |
| Arm/Group Title | Dabigatran 150 mg | Warfarin |
|---|---|---|
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 |
| Measure Participants | 1204 | 1198 |
| AST increase |
21
1.6%
|
22
1.7%
|
| AST decrease |
0
0%
|
0
0%
|
| ALT increase |
26
2%
|
38
3%
|
| ALT decrease |
0
0%
|
0
0%
|
| Bilirubin increase |
7
0.5%
|
13
1%
|
| Bilirubin decrease |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Dabigatran 150 mg | Warfarin | ||
| Arm/Group Description | bid (twice daily) oral | PRN to maintain an INR of 2.0-3.0 | ||
All Cause Mortality |
||||
| Dabigatran 150 mg | Warfarin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Dabigatran 150 mg | Warfarin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 165/1273 (13%) | 150/1266 (11.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 5/1273 (0.4%) | 2/1266 (0.2%) | ||
| Febrile neutropenia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Iron deficiency anaemia | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Cardiac disorders | ||||
| Acute coronary syndrome | 0/1273 (0%) | 2/1266 (0.2%) | ||
| Acute myocardial infarction | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Angina pectoris | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Angina unstable | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Arrhythmia | 0/1273 (0%) | 2/1266 (0.2%) | ||
| Atrial fibrillation | 2/1273 (0.2%) | 2/1266 (0.2%) | ||
| Atrioventricular block | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Bradyarrhythmia | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Cardiac arrest | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Cardiac failure | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Cardiopulmonary failure | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Coronary artery disease | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Coronary artery occlusion | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Left ventricular failure | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Myocardial infarction | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Myocardial ischaemia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Pericardial effusion | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Ear and labyrinth disorders | ||||
| Ear haemorrhage | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Middle ear inflammation | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Vertigo | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Endocrine disorders | ||||
| Goitre | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Eye disorders | ||||
| Optic ischaemic neuropathy | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Abdominal symptom | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Colonic polyp | 2/1273 (0.2%) | 1/1266 (0.1%) | ||
| Crohn's disease | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Diarrhoea | 0/1273 (0%) | 2/1266 (0.2%) | ||
| Duodenal ulcer | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Duodenal ulcer haemorrhage | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Faeces discoloured | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Gastric ulcer | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Gastritis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Gastrointestinal disorder | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Gastrointestinal haemorrhage | 1/1273 (0.1%) | 3/1266 (0.2%) | ||
| Gastrooesophageal reflux disease | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Gingival bleeding | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Haematemesis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Inguinal hernia | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Intestinal obstruction | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Nausea | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Oesophageal haemorrhage | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Oesophageal ulcer | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Pancreatic mass | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Pneumoperitoneum | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Rectal haemorrhage | 6/1273 (0.5%) | 1/1266 (0.1%) | ||
| Small intestinal haemorrhage | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Small intestinal obstruction | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Vomiting | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| General disorders | ||||
| Asthenia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Chest discomfort | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Chest pain | 4/1273 (0.3%) | 6/1266 (0.5%) | ||
| Death | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Drug ineffective | 1/1273 (0.1%) | 0/1266 (0%) | ||
| General physical health deterioration | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Haemorrhagic cyst | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Multi-organ failure | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Non-cardiac chest pain | 4/1273 (0.3%) | 0/1266 (0%) | ||
| Oedema | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Oedema peripheral | 1/1273 (0.1%) | 4/1266 (0.3%) | ||
| Polyp | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Pseudocyst | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Pyrexia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Hepatobiliary disorders | ||||
| Bile duct obstruction | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Bile duct stone | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Cholangitis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Cholecystitis | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Cholecystitis acute | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Cholecystitis chronic | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Cholelithiasis | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Hepatic cirrhosis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Hepatic necrosis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Hepatitis fulminant | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Hydrocholecystis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Immune system disorders | ||||
| Sarcoidosis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Infections and infestations | ||||
| Abscess | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Anal abscess | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Bronchitis | 2/1273 (0.2%) | 1/1266 (0.1%) | ||
| Bronchopneumonia | 3/1273 (0.2%) | 0/1266 (0%) | ||
| Cellulitis | 2/1273 (0.2%) | 3/1266 (0.2%) | ||
| Empyema | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Erysipelas | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Gastroenteritis | 5/1273 (0.4%) | 0/1266 (0%) | ||
| Labyrinthitis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Lobar pneumonia | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Lower respiratory tract infection | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Lung abscess | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Peritoneal infection | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Pneumonia | 5/1273 (0.4%) | 8/1266 (0.6%) | ||
| Pyelonephritis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Respiratory tract infection | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Sepsis | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Sinusitis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Subcutaneous abscess | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Tonsillitis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Urinary tract infection | 2/1273 (0.2%) | 2/1266 (0.2%) | ||
| Vestibular neuronitis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Wound sepsis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Injury, poisoning and procedural complications | ||||
| Abdominal injury | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Fall | 0/1273 (0%) | 2/1266 (0.2%) | ||
| Femur fracture | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Graft thrombosis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Hip fracture | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Joint dislocation | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Joint injury | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Limb injury | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Lower limb fracture | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Multiple injuries | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Post procedural haematuria | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Radius fracture | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Rib fracture | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Road traffic accident | 2/1273 (0.2%) | 1/1266 (0.1%) | ||
| Synovial rupture | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Tibia fracture | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Traumatic haematoma | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Vascular pseudoaneurysm | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Vascular pseudoaneurysm ruptured | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Aspartate aminotransferase increased | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Biopsy bladder | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Cardiac imaging procedure abnormal | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Haemoglobin decreased | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Hepatic enzyme increased | 1/1273 (0.1%) | 0/1266 (0%) | ||
| International normalised ratio increased | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Investigation | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Liver function test abnormal | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Troponin I increased | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Dehydration | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Diabetes mellitus | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Diabetes mellitus inadequate control | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Hypoalbuminaemia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Hypoglycaemia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Hypokalaemia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 2/1273 (0.2%) | 1/1266 (0.1%) | ||
| Bone pain | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Chondrocalcinosis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Fibromyalgia | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Flank pain | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Fracture nonunion | 0/1273 (0%) | 2/1266 (0.2%) | ||
| Haemarthrosis | 0/1273 (0%) | 3/1266 (0.2%) | ||
| Jaw cyst | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Muscle haemorrhage | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Musculoskeletal pain | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Myalgia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Osteoarthritis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Osteochondrosis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Pain in extremity | 1/1273 (0.1%) | 2/1266 (0.2%) | ||
| Spinal osteoarthritis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute myeloid leukaemia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| B-cell lymphoma recurrent | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Bladder cancer | 0/1273 (0%) | 2/1266 (0.2%) | ||
| Breast cancer | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Cervix carcinoma recurrent | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Colon cancer | 2/1273 (0.2%) | 2/1266 (0.2%) | ||
| Fibroadenoma of breast | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Gallbladder cancer | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Gastrointestinal carcinoma | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Hepatic neoplasm malignant | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Lung adenocarcinoma | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Lung neoplasm malignant | 0/1273 (0%) | 2/1266 (0.2%) | ||
| Malignant melanoma | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Malignant neoplasm progression | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Malignant pleural effusion | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Metastases to adrenals | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Metastases to liver | 5/1273 (0.4%) | 2/1266 (0.2%) | ||
| Metastases to lung | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Metastases to lymph nodes | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Metastases to spleen | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Metastases to the mediastinum | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Metastatic malignant melanoma | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Metastatic neoplasm | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Oesophageal carcinoma | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Ovarian cancer metastatic | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Ovarian epithelial cancer | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Pancreatic carcinoma | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Prostate cancer | 1/1273 (0.1%) | 2/1266 (0.2%) | ||
| Prostatic adenoma | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Renal cancer | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Renal cell carcinoma | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Renal neoplasm | 2/1273 (0.2%) | 1/1266 (0.1%) | ||
| Sarcoma | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Uterine cancer | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Nervous system disorders | ||||
| Acute polyneuropathy | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Cerebellar haemorrhage | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Cerebral ischaemia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Convulsion | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Dizziness | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Dizziness postural | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Epilepsy | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Haemorrhage intracranial | 0/1273 (0%) | 2/1266 (0.2%) | ||
| Headache | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Hemiparesis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Ischaemic stroke | 3/1273 (0.2%) | 0/1266 (0%) | ||
| Migraine | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Polyneuropathy | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Presyncope | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Somnolence | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Speech disorder | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Subdural hygroma | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Syncope | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Transient ischaemic attack | 2/1273 (0.2%) | 1/1266 (0.1%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion incomplete | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Psychiatric disorders | ||||
| Anxiety | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Depression | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Renal and urinary disorders | ||||
| Calculus ureteric | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Calculus urinary | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Haematuria | 4/1273 (0.3%) | 9/1266 (0.7%) | ||
| Renal colic | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Renal failure | 2/1273 (0.2%) | 1/1266 (0.1%) | ||
| Renal failure acute | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Renal vein thrombosis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Urethral stenosis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Urinary retention | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Reproductive system and breast disorders | ||||
| Bartholinitis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Breast haemorrhage | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Endometriosis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Metrorrhagia | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Prostatitis | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Asthma | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Chronic obstructive pulmonary disease | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Cough | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Dyspnoea | 5/1273 (0.4%) | 10/1266 (0.8%) | ||
| Epistaxis | 1/1273 (0.1%) | 2/1266 (0.2%) | ||
| Haemoptysis | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Haemothorax | 1/1273 (0.1%) | 2/1266 (0.2%) | ||
| Hydropneumothorax | 0/1273 (0%) | 2/1266 (0.2%) | ||
| Hyperventilation | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Lung disorder | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Lung infiltration | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Pleural effusion | 3/1273 (0.2%) | 2/1266 (0.2%) | ||
| Pleural fibrosis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Pleurisy | 1/1273 (0.1%) | 2/1266 (0.2%) | ||
| Pneumonia aspiration | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Pneumothorax | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Pulmonary embolism | 14/1273 (1.1%) | 7/1266 (0.6%) | ||
| Pulmonary infarction | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Pulmonary oedema | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Respiratory failure | 2/1273 (0.2%) | 0/1266 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Angioedema | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Erythema | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Erythema nodosum | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Leukocytoclastic vasculitis | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Surgical and medical procedures | ||||
| Abortion induced | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Vascular disorders | ||||
| Accelerated hypertension | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Arterial thrombosis limb | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Deep vein thrombosis | 10/1273 (0.8%) | 9/1266 (0.7%) | ||
| Haematoma | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Haemorrhage | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Hypotension | 0/1273 (0%) | 1/1266 (0.1%) | ||
| Iliac artery thrombosis | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Lymphoedema | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Peripheral artery aneurysm | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Peripheral ischaemia | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Post thrombotic syndrome | 1/1273 (0.1%) | 1/1266 (0.1%) | ||
| Shock haemorrhagic | 1/1273 (0.1%) | 0/1266 (0%) | ||
| Thrombosis | 0/1273 (0%) | 1/1266 (0.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Dabigatran 150 mg | Warfarin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 163/1273 (12.8%) | 209/1266 (16.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 63/1273 (4.9%) | 69/1266 (5.5%) | ||
| Nervous system disorders | ||||
| Headache | 78/1273 (6.1%) | 87/1266 (6.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Epistaxis | 35/1273 (2.7%) | 78/1266 (6.2%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Any publication of the results of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Results Point of Contact
| Name/Title | Boehringer Ingelheim Call Center |
|---|---|
| Organization | Boehringer Ingelheim Pharmaceuticals |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00291330
Other Study ID Numbers:
- 1160.53
- 2005-001999-12
First Posted:
Feb 14, 2006
Last Update Posted:
Jun 6, 2014
Last Verified:
Apr 1, 2014