Thromboembolism
Conditions
Brief summary
The general aim of this study is to determine the comparative safety and efficacy of dabigatran etexilate administered orally and warfarin (International Normalized Ratio (INR) of 2.0-3.0) for the long-term treatment and secondary prevention of symptomatic venous thromboembolism in patients who have been successfully treated with standard doses of an approved anticoagulant for three to twelve months for confirmed acute symptomatic Venous Thrombo-embolism.
Interventions
DRUGDabigatran
Dabigatran 150 mg BID (twice daily)
DRUGWarfarin
Warfarin dosed individually to maintain INR 2.0-3.0
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion\_Criteria * Acute symptomatic deep vein thrombosis (DVT) * Pulmonary embolism (PE) 3-12 months prior to screening, which has been documented by objective testing
Exclusion criteria
Exclusion\_Criteria * Symptomatic DVT or PE at screening Interruption of anticoagulant therapy for 2 or more weeks during the 3-12 months of treatment for the prior VTE. * Patients who in the investigators judgement are perceived as having an excessive risk of bleeding Elevated Aspartate aminotransferase (AST) or Alanine tranminase (ALT) \> 2x ULN * Severe renal impairment (estimated creatinine clearance \<= 30 ml/min)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of Recurrent VTE or VTE Death at 36 Months | 36 months | Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and death related to VTE. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation. In case of death, autopsy was an additional way to confirm VTE. |
| Composite of Recurrent VTE or VTE Death at 18 Months | 18 months | Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and death related to VTE. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation. In case of death, autopsy was an additional way to confirm VTE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Deep Vein Thrombosis (DVT) at 36 Months | 36 months | Symptomatic Deep vein thrombosis (DVT). All DVT events required objective verification through definitive diagnostic evaluation. |
| DVT at 18 Months | 18 months | Symptomatic Deep vein thrombosis (DVT). All DVT events required objective verification through definitive diagnostic evaluation. |
| Symptomatic Pulmonary Embolism (PE) at 36 Months | 36 months | Symptomatic pulmonary embolism (PE) at 36 Months (fatal or non-fatal). All suspected PEs required confirmation by one of the following: ventilation-perfusion (V-Q) lung scan, pulmonary angiography, or spiral (helical) Computed tomography. |
| Symptomatic Pulmonary Embolism (PE) at 18 Months | 18 months | Symptomatic pulmonary embolism (PE) at 18 Months (fatal or non-fatal). All suspected PEs required confirmation by one of the following: ventilation-perfusion (V-Q) lung scan, pulmonary angiography, or spiral (helical) Computed tomography. |
| Deaths Related to VTE at 36 Months | 36 months | Deaths related to VTE (i.e. fatal PE) at 36 Months. Deaths related to VTE (i.e. fatal PE) at 18 Months. All deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death in a treatment-blinded way. |
| Composite of Recurrent VTE or All Cause Death at 36 Months | 36 months | Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and all cause death. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation. |
| Deaths of All Causes at 36 Months | 36 months | Deaths of all causes at 36 Months. All components of the primary efficacy endpoint and all deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death without knowledge of any individual treatment assignments. |
| Deaths of All Causes at 18 Months | 18 months | Deaths of all causes at 18 Months. All components of the primary efficacy endpoint and all deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death without knowledge of any individual treatment assignments. |
| Number of Participants With Bleeding Events | first intake of study drug until 6 days following last intake of study drug | MBE (major bleeding event) if it fulfilled at least one of the following criteria * 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. Minor bleeding event was any bleeding that did not fulfil any of the criteria for MBEs CRBE (clinically relevant bleeding event) if it is a minor bleeding events which fulfilled at least one of the following criteria * Spontaneous skin haematoma ≥25 cm2 * Spontaneous nose bleed \>5 min duration * Macroscopic haematuria, either spontaneous or, if associated with an intervention, lasting \>24 h * Spontaneous rectal bleeding * Gingival bleeding \>5 min * Bleeding leading to hospitalisation or requiring surgical treatment * Bleeding leading to a transfusion of \<2 units of whole blood or red cells * Any other bleeding event considered clinically relevant by the investigator |
| Laboratory Analysis | 18 months + 30 days follow up | Patients with LFT (liver function tests) increases of possible clinical significance during treatment. Increases of possible clinical significance were defined as: ≥3 x ULN (AST, ALT), ≥2 x ULN (AP), and ≥2 mg/dL (total bilirubin). Only patients with a baseline value which was not of possible clinical significance (or without any baseline value) could have a PCSA (Possible clinically significant abnormality). |
| Number of Participants With Definite Acute Coronary Syndrome (ACS) | day of first study drug intake until last day of study drug intake; from the day after last intake of study drug until trial termination | All suspected ACS occurring during the trial were to be recorded on the CRF and were to be centrally adjudicated by an independent ACS/AC in a treatment-blinded manner. |
| Deaths Related to VTE at 18 Months | 18 months | Deaths related to VTE (i.e. fatal PE) at 18 Months. All deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death in a treatment-blinded way. |
| Composite of Recurrent VTE or All Cause Death at 18 Months | 18 months | Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and all cause death. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Russia, Slovakia, South Africa, Spain, Sweden, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran 150 mg twice daily, total daily dose 300 mg | 1,430 |
| Warfarin Target International Normalized Ratio (INR) of 2.0 to 3.0 | 1,426 |
| Total | 2,856 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 147 | 129 |
| Overall Study | Lost to Follow-up | 2 | 6 |
| Overall Study | Other reason (not specified) | 40 | 54 |
| Overall Study | Protocol Violation | 23 | 34 |
| Overall Study | Withdrawal by Subject | 64 | 58 |
Baseline characteristics
| Characteristic | Dabigatran | Warfarin | Total |
|---|---|---|---|
| Age, Continuous | 55.38 years STANDARD_DEVIATION 14.99 | 53.90 years STANDARD_DEVIATION 15.34 | 54.64 years STANDARD_DEVIATION 15.18 |
| Age, Customized >=18 to <40 years | 237 participants | 269 participants | 506 participants |
| Age, Customized >=40 to <50 years | 250 participants | 291 participants | 541 participants |
| Age, Customized >=50 to <65 years | 500 participants | 459 participants | 959 participants |
| Age, Customized >=65 to <75 years | 303 participants | 288 participants | 591 participants |
| Age, Customized >= 75 years | 140 participants | 119 participants | 259 participants |
| Body Mass Index (BMI) | 29.15 kg/square meter STANDARD_DEVIATION 5.65 | 29.01 kg/square meter STANDARD_DEVIATION 5.75 | 29.08 kg/square meter STANDARD_DEVIATION 5.7 |
| Body Mass Index (BMI) category <25 kg/square meter | 315 Participants | 334 Participants | 649 Participants |
| Body Mass Index (BMI) category >=25 to <30 kg/square meter | 571 Participants | 584 Participants | 1155 Participants |
| Body Mass Index (BMI) category >=30 to <35 kg/square meter | 356 Participants | 330 Participants | 686 Participants |
| Body Mass Index (BMI) category >= 35 kg/square meter | 186 Participants | 174 Participants | 360 Participants |
| Body Mass Index (BMI) category Missing | 2 Participants | 4 Participants | 6 Participants |
| Height | 171.55 cm STANDARD_DEVIATION 9.73 | 171.95 cm STANDARD_DEVIATION 10.08 | 171.75 cm STANDARD_DEVIATION 9.9 |
| Race/Ethnicity, Customized Asian | 113 Participants | 114 Participants | 227 Participants |
| Race/Ethnicity, Customized Black | 29 Participants | 28 Participants | 57 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 105 Participants | 109 Participants | 214 Participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 1325 Participants | 1317 Participants | 2642 Participants |
| Race/Ethnicity, Customized White | 1288 Participants | 1284 Participants | 2572 Participants |
| Serum creatinine clearance | 104.2 mL/min STANDARD_DEVIATION 38.6 | 106.6 mL/min STANDARD_DEVIATION 37.9 | 105.4 mL/min STANDARD_DEVIATION 38.3 |
| Serum creatinine clearance category >=0 to <30 mL/min | 0 Participants | 4 Participants | 4 Participants |
| Serum creatinine clearance category >=30 to <50 mL/min | 59 Participants | 45 Participants | 104 Participants |
| Serum creatinine clearance category >=50 to <80 mL/min | 328 Participants | 289 Participants | 617 Participants |
| Serum creatinine clearance category >= 80 mL/min | 1031 Participants | 1072 Participants | 2103 Participants |
| Serum creatinine clearance category Missing | 12 Participants | 16 Participants | 28 Participants |
| Sex: Female, Male Female | 559 Participants | 555 Participants | 1114 Participants |
| Sex: Female, Male Male | 871 Participants | 871 Participants | 1742 Participants |
| Smoking history Current smoker | 223 Participants | 231 Participants | 454 Participants |
| Smoking history Ex-smoker | 393 Participants | 366 Participants | 759 Participants |
| Smoking history Non-smoker | 814 Participants | 829 Participants | 1643 Participants |
| Weight | 86.09 kg STANDARD_DEVIATION 19.26 | 85.95 kg STANDARD_DEVIATION 18.87 | 86.02 kg STANDARD_DEVIATION 19.06 |
| Weight category >= 100 kg | 299 Participants | 300 Participants | 599 Participants |
| Weight category < 50 kg | 10 Participants | 5 Participants | 15 Participants |
| Weight category >= 50 to < 100 kg | 1120 Participants | 1117 Participants | 2237 Participants |
| Weight category Missing | 1 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 409 / 1,430 | 415 / 1,426 | 34 / 1,395 | 32 / 1,384 |
| serious Total, serious adverse events | 227 / 1,430 | 224 / 1,426 | 33 / 1,395 | 41 / 1,384 |
Outcome results
Primary
Composite of Recurrent VTE or VTE Death at 18 Months
Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and death related to VTE. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation. In case of death, autopsy was an additional way to confirm VTE.
Time frame: 18 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Composite of Recurrent VTE or VTE Death at 18 Months | Number of participants with event | 22 Participants |
| Dabigatran | Composite of Recurrent VTE or VTE Death at 18 Months | Number of participants with no event | 1408 Participants |
| Warfarin | Composite of Recurrent VTE or VTE Death at 18 Months | Number of participants with event | 17 Participants |
| Warfarin | Composite of Recurrent VTE or VTE Death at 18 Months | Number of participants with no event | 1409 Participants |
p-value: <0.000195% CI: [-0.5, 1.25]Regression, Cox
p-value: 0.4013Kaplan-Meier
Primary
Composite of Recurrent VTE or VTE Death at 36 Months
Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and death related to VTE. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation. In case of death, autopsy was an additional way to confirm VTE.
Time frame: 36 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Composite of Recurrent VTE or VTE Death at 36 Months | Number of participants with event | 26 Participants |
| Dabigatran | Composite of Recurrent VTE or VTE Death at 36 Months | Number of participants with no event | 1404 Participants |
| Warfarin | Composite of Recurrent VTE or VTE Death at 36 Months | Number of participants with event | 18 Participants |
| Warfarin | Composite of Recurrent VTE or VTE Death at 36 Months | Number of participants with no event | 1408 Participants |
p-value: 0.013795% CI: [0.78, 2.64]Regression, Cox
p-value: 0.2424Regression, Cox
Secondary
Composite of Recurrent VTE or All Cause Death at 18 Months
Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and all cause death. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation.
Time frame: 18 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Composite of Recurrent VTE or All Cause Death at 18 Months | Number of participants with no event | 1394 Participants |
| Dabigatran | Composite of Recurrent VTE or All Cause Death at 18 Months | Number of participants with event | 36 Participants |
| Warfarin | Composite of Recurrent VTE or All Cause Death at 18 Months | Number of participants with event | 32 Participants |
| Warfarin | Composite of Recurrent VTE or All Cause Death at 18 Months | Number of participants with no event | 1394 Participants |
Comparison: Dabigatran versus Warfarinp-value: 0.887695% CI: [-1.11, 1.28]Kaplan-Meier
Secondary
Composite of Recurrent VTE or All Cause Death at 36 Months
Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and all cause death. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation.
Time frame: 36 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Composite of Recurrent VTE or All Cause Death at 36 Months | Number of participants with event | 42 Participants |
| Dabigatran | Composite of Recurrent VTE or All Cause Death at 36 Months | Number of participants with no event | 1388 Participants |
| Warfarin | Composite of Recurrent VTE or All Cause Death at 36 Months | Number of participants with event | 36 Participants |
| Warfarin | Composite of Recurrent VTE or All Cause Death at 36 Months | Number of participants with no event | 1390 Participants |
p-value: 0.473295% CI: [0.75, 1.84]Regression, Cox
Secondary
Deaths of All Causes at 18 Months
Deaths of all causes at 18 Months. All components of the primary efficacy endpoint and all deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death without knowledge of any individual treatment assignments.
Time frame: 18 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Deaths of All Causes at 18 Months | Number of participants with event | 15 Participants |
| Dabigatran | Deaths of All Causes at 18 Months | Number of participants with no event | 1415 Participants |
| Warfarin | Deaths of All Causes at 18 Months | Number of participants with event | 16 Participants |
| Warfarin | Deaths of All Causes at 18 Months | Number of participants with no event | 1410 Participants |
Comparison: Dabigatran versus Warfarinp-value: 0.962295% CI: [-0.89, 0.84]Kaplan-Meier
Secondary
Deaths of All Causes at 36 Months
Deaths of all causes at 36 Months. All components of the primary efficacy endpoint and all deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death without knowledge of any individual treatment assignments.
Time frame: 36 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Deaths of All Causes at 36 Months | Number of participants with event | 17 Participants |
| Dabigatran | Deaths of All Causes at 36 Months | Number of participants with no event | 1413 Participants |
| Warfarin | Deaths of All Causes at 36 Months | Number of participants with event | 19 Participants |
| Warfarin | Deaths of All Causes at 36 Months | Number of participants with no event | 1407 Participants |
Comparison: Dabigatran versus Warfarinp-value: 0.740595% CI: [0.47, 1.72]Regression, Cox
Secondary
Deaths Related to VTE at 18 Months
Deaths related to VTE (i.e. fatal PE) at 18 Months. All deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death in a treatment-blinded way.
Time frame: 18 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Deaths Related to VTE at 18 Months | Number of participants with event | 1 Participants |
| Dabigatran | Deaths Related to VTE at 18 Months | Number of participants with no event | 1429 Participants |
| Warfarin | Deaths Related to VTE at 18 Months | Number of participants with event | 1 Participants |
| Warfarin | Deaths Related to VTE at 18 Months | Number of participants with no event | 1425 Participants |
Comparison: Dabigatran versus Warfarinp-value: 0.920495% CI: [-0.2, 0.23]Kaplan-Meier
Secondary
Deaths Related to VTE at 36 Months
Deaths related to VTE (i.e. fatal PE) at 36 Months. Deaths related to VTE (i.e. fatal PE) at 18 Months. All deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death in a treatment-blinded way.
Time frame: 36 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Deaths Related to VTE at 36 Months | Number of participants with event | 1 Participants |
| Dabigatran | Deaths Related to VTE at 36 Months | Number of participants with no event | 1429 Participants |
| Warfarin | Deaths Related to VTE at 36 Months | Number of participants with event | 1 Participants |
| Warfarin | Deaths Related to VTE at 36 Months | Number of participants with no event | 1425 Participants |
Comparison: Dabigatran versus Warfarinp-value: 0.992195% CI: [0.06, 16.22]Regression, Cox
Secondary
Deep Vein Thrombosis (DVT) at 36 Months
Symptomatic Deep vein thrombosis (DVT). All DVT events required objective verification through definitive diagnostic evaluation.
Time frame: 36 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Deep Vein Thrombosis (DVT) at 36 Months | Number of participants with event | 17 Participants |
| Dabigatran | Deep Vein Thrombosis (DVT) at 36 Months | Number of participants with no event | 1413 Participants |
| Warfarin | Deep Vein Thrombosis (DVT) at 36 Months | Number of participants with event | 13 Participants |
| Warfarin | Deep Vein Thrombosis (DVT) at 36 Months | Number of participants with no event | 1413 Participants |
Comparison: Dabigatran versus Warfarinp-value: 0.454895% CI: [0.64, 2.71]Regression, Cox
Secondary
DVT at 18 Months
Symptomatic Deep vein thrombosis (DVT). All DVT events required objective verification through definitive diagnostic evaluation.
Time frame: 18 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | DVT at 18 Months | Number of participants with event | 15 Participants |
| Dabigatran | DVT at 18 Months | Number of participants with no event | 1415 Participants |
| Warfarin | DVT at 18 Months | Number of participants with event | 12 Participants |
| Warfarin | DVT at 18 Months | Number of participants with no event | 1414 Participants |
Comparison: Dabigatran versus Warfarinp-value: 0.656395% CI: [-0.63, 1]Kaplan-Meier
Secondary
Laboratory Analysis
Patients with LFT (liver function tests) increases of possible clinical significance during treatment. Increases of possible clinical significance were defined as: ≥3 x ULN (AST, ALT), ≥2 x ULN (AP), and ≥2 mg/dL (total bilirubin). Only patients with a baseline value which was not of possible clinical significance (or without any baseline value) could have a PCSA (Possible clinically significant abnormality).
Time frame: 18 months + 30 days follow up
Population: FAS as treated
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Laboratory Analysis | ALT increase | 26 participants |
| Dabigatran | Laboratory Analysis | AST increase | 23 participants |
| Dabigatran | Laboratory Analysis | Alkaline phosphatase | 9 participants |
| Dabigatran | Laboratory Analysis | Total bilirubin | 9 participants |
| Warfarin | Laboratory Analysis | Total bilirubin | 8 participants |
| Warfarin | Laboratory Analysis | ALT increase | 30 participants |
| Warfarin | Laboratory Analysis | Alkaline phosphatase | 14 participants |
| Warfarin | Laboratory Analysis | AST increase | 23 participants |
Secondary
Number of Participants With Bleeding Events
MBE (major bleeding event) if it fulfilled at least one of the following criteria * 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. Minor bleeding event was any bleeding that did not fulfil any of the criteria for MBEs CRBE (clinically relevant bleeding event) if it is a minor bleeding events which fulfilled at least one of the following criteria * Spontaneous skin haematoma ≥25 cm2 * Spontaneous nose bleed \>5 min duration * Macroscopic haematuria, either spontaneous or, if associated with an intervention, lasting \>24 h * Spontaneous rectal bleeding * Gingival bleeding \>5 min * Bleeding leading to hospitalisation or requiring surgical treatment * Bleeding leading to a transfusion of \<2 units of whole blood or red cells * Any other bleeding event considered clinically relevant by the investigator
Time frame: first intake of study drug until 6 days following last intake of study drug
Population: FAS as treated
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Number of Participants With Bleeding Events | patients with MBE | 13 participants |
| Dabigatran | Number of Participants With Bleeding Events | patients with MBE and /or CRBE | 80 participants |
| Dabigatran | Number of Participants With Bleeding Events | patients with any bleeding event | 277 participants |
| Warfarin | Number of Participants With Bleeding Events | patients with MBE | 25 participants |
| Warfarin | Number of Participants With Bleeding Events | patients with MBE and /or CRBE | 145 participants |
| Warfarin | Number of Participants With Bleeding Events | patients with any bleeding event | 373 participants |
Comparison: Hazard ratio estimated using the Cox regression with treatment, cohort, baseline stratification factors (including active cancer at baseline and symptomatic PE as qualifying event) and their interaction.p-value: 0.057795% CI: [0.27, 1.02]Regression, Cox
Comparison: Hazard ratio estimated using the Cox regression with treatment, cohort, baseline stratification factors (including active cancer at baseline and symptomatic PE as qualifying event) and their interaction.p-value: <0.000195% CI: [0.61, 0.83]Regression, Cox
Secondary
Number of Participants With Definite Acute Coronary Syndrome (ACS)
All suspected ACS occurring during the trial were to be recorded on the CRF and were to be centrally adjudicated by an independent ACS/AC in a treatment-blinded manner.
Time frame: day of first study drug intake until last day of study drug intake; from the day after last intake of study drug until trial termination
Population: FAS as treated
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Number of Participants With Definite Acute Coronary Syndrome (ACS) | During intake of study drug, N=1430 , N=1415 | 12 participants |
| Dabigatran | Number of Participants With Definite Acute Coronary Syndrome (ACS) | After stopping study drug, N=1426, N=1400 | 1 participants |
| Warfarin | Number of Participants With Definite Acute Coronary Syndrome (ACS) | During intake of study drug, N=1430 , N=1415 | 2 participants |
| Warfarin | Number of Participants With Definite Acute Coronary Syndrome (ACS) | After stopping study drug, N=1426, N=1400 | 5 participants |
Secondary
Symptomatic Pulmonary Embolism (PE) at 18 Months
Symptomatic pulmonary embolism (PE) at 18 Months (fatal or non-fatal). All suspected PEs required confirmation by one of the following: ventilation-perfusion (V-Q) lung scan, pulmonary angiography, or spiral (helical) Computed tomography.
Time frame: 18 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Symptomatic Pulmonary Embolism (PE) at 18 Months | Number of participants with event | 8 Participants |
| Dabigatran | Symptomatic Pulmonary Embolism (PE) at 18 Months | Number of participants with no event | 1422 Participants |
| Warfarin | Symptomatic Pulmonary Embolism (PE) at 18 Months | Number of participants with event | 5 Participants |
| Warfarin | Symptomatic Pulmonary Embolism (PE) at 18 Months | Number of participants with no event | 1421 Participants |
Comparison: Dabigatran versus Warfarinp-value: 0.372395% CI: [-0.32, 0.84]Kaplan-Meier
Secondary
Symptomatic Pulmonary Embolism (PE) at 36 Months
Symptomatic pulmonary embolism (PE) at 36 Months (fatal or non-fatal). All suspected PEs required confirmation by one of the following: ventilation-perfusion (V-Q) lung scan, pulmonary angiography, or spiral (helical) Computed tomography.
Time frame: 36 months
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran | Symptomatic Pulmonary Embolism (PE) at 36 Months | Number of participants with event | 10 Participants |
| Dabigatran | Symptomatic Pulmonary Embolism (PE) at 36 Months | Number of participants with no event | 1420 Participants |
| Warfarin | Symptomatic Pulmonary Embolism (PE) at 36 Months | Number of participants with event | 5 Participants |
| Warfarin | Symptomatic Pulmonary Embolism (PE) at 36 Months | Number of participants with no event | 1421 Participants |
Comparison: Dabigatran versus Warfarinp-value: 0.192595% CI: [0.7, 5.98]Regression, Cox