Atrial Fibrillation
Conditions
Brief summary
The primary objective was to evaluate the safety of dabigatran etexilate(BIBR 1048) administered orally at doses of 110 and 150 mg, twice daily, for 12 weeks in patients with non-valvular atrial fibrillation (paroxysmal, persistent or permanent) in comparison with warfarin.
Interventions
DRUGDabigatran etexilate
Dabigatran etexilate 110 mg capsule, twice a day, oral administration
DRUGWarfarin
Dose-adjusted warfarin based on target INR values
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria 1. Patients with non-valvular atrial fibrillation (paroxysmal, persistent or permanent) 2. Patients who had additional risk factor for thromboembolism; one or more of the following conditions/events: * Hypertension * Diabetes mellitus * Left-side heart failure * A previous ischemic stroke or transient ischemic attack * Age 75 years or older * A history of coronary artery diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency (Occurrence Rates) of Major Bleeding Event | upto 15 weeks | The percentage of patients with major bleeding event. Major bleeding was defined as any bleed fulfilling one of the following conditions: * Fatal or life-threatening * Retroperitoneal, intracranial, intraocular, or intraspinal bleeding (verified by objective testing) * Bleeding requiring surgical treatment * Clinically overt bleeding leading to a transfusion (erythrocyte component transfusion or whole blood transfusion) of 4.5 units (equal to 2 units in EU/US) or more * Clinically overt bleeding leading to a fall in haemoglobin of at least 2 g/dL |
| Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event | upto 15 weeks | The percentage of patients with clinically relevant bleeding event. Any bleed that did not qualify as a major bleed was defined as a minor bleed; minor bleed which fulfilled one of the criteria below was defined as a clinically relevant bleeding event: * A skin haematoma of at least 25 sqcm * Spontaneous nose bleed lasting for more than 5 minutes * Macroscopic haematuria (either spontaneous or, if associated with an intervention, lasting more than 24 hours) * Spontaneous rectal bleeding (more than spotting on toilet paper) * Gingival bleeding lasting for more than 5 minutes * Bleeding leading to hospitalisation * Bleeding leading to blood transfusion (erythrocyte component transfusion or whole blood transfusion) of less than 4.5 units (equal to 2 units in EU/US) * Any other bleeding considered clinically relevant by the investigator |
| Frequency (Occurrence Rates) of Nuisance Bleeding Event | Upto 15 weeks | The percentage of patients with nuisance bleeding event Any bleed that did not qualify as a major bleed was defined as a minor bleed; all minor bleeding events not fulfilling one of the criteria below was defined as a nuisance bleeding event: * A skin haematoma of at least 25 sqcm * Spontaneous nose bleed lasting for more than 5 minutes * Macroscopic haematuria (either spontaneous or, if associated with an intervention, lasting more than 24 hours) * Spontaneous rectal bleeding (more than spotting on toilet paper) * Gingival bleeding lasting for more than 5 minutes * Bleeding leading to hospitalisation * Bleeding leading to blood transfusion (erythrocyte component transfusion or whole blood transfusion) of less than 4.5 units (equal to 2 units in EU/US) * Any other bleeding considered clinically relevant by the investigator |
| Incidence and Severity of Adverse Events | Upto 15 weeks | Intensity of event is categorised as mild, moderate and severe. |
| Discontinuation of the Study Drug Due to Adverse Events | Upto 15 weeks | Discontinuation of the study drug due to adverse events. |
| Changes in Laboratory Test Values | 12 weeks | The number of patients with ALT, AST, alkaline phosphatase, or bilirubin exceeded the upper limit of normal (ULN) range |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency (Occurrence Rates) of Death | Upto 15 weeks | The percentage of patients with death |
| Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) | Week 0,1,4 and 12 | The blood coagulation parameter aPTT was assessed in patients allocated to the dabigatran etexilate groups at week 0, prior to drug administration and at the trough at week 1, 4 and 12. |
| Anticoagulation Effects Trough ECT (Ecarin Clotting Time) | Week 0,1,4 and 12 | The blood coagulation parameter ECT was assessed in patients allocated to the dabigatran etexilate groups at week 0, prior to drug administration and at the trough at week 1, 4 and 12. |
| Frequency (Occurrence Rates) of a Composite Clinical Endpoint. | Upto 15 weeks | Percentage of patients with the composite clinical endpoint (ischemic or haemorrhagic stroke (fatal or non-fatal), transient ischemic attacks, systemic embolism, myocardial infarction (fatal or non-fatal), other major adverse cardiac events, and death) |
| Anticoagulation Effects Trough 11-dehydrothromboxane B2 | Week 0 and 12 | Analysis based on concomitant use of aspirin compared to no aspirin users. 11-dehydrothromboxane B2 is measured in urine of patients. |
| Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration | Week 1,4 and 12 | — |
| Anticoagulation Effects Trough INR (International Normalised Ratio) | Week 0,1,4 and 12 | The blood coagulation parameter INR was assessed in patients allocated to the dabigatran etexilate groups at week 0, prior to drug administration and at the trough at week 1, 4 and 12. |
| Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal) | Upto 15 weeks | The percentage of patients with ischemic or haemorrhagic stroke (fatal or non-fatal) |
| Frequency (Occurrence Rates) of Transient Ischemic Attack | Upto 15 weeks | The percentage of patients with transient ischemic attack |
| Frequency (Occurrence Rates) of Systemic Embolism | Upto 15 weeks | The percentage of patients with systemic embolism |
| Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal) | Upto 15 weeks | The percentage of patients with myocardial infarction (fatal or non-fatal) |
| Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events | Upto 15 weeks | The percentage of patients with other major adverse cardiac events |
Countries
Japan
Participant flow
Recruitment details
Eight patients were randomised but not treated with study drug, hence resulting in 174 patients as enrolled and 166 who were actually treated.
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran Etexilate 220 mg Daily Dabigatran etexilate 110 mg capsule, twice a day, oral administration | 46 |
| Dabigatran Etexilate 300 mg Daily Dabigatran etexilate 150 mg capsule, twice a day, oral administration | 58 |
| Warfarin Dose-adjusted warfarin based on target INR values | 62 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 8 | 4 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Dabigatran Etexilate 220 mg Daily | Dabigatran Etexilate 300 mg Daily | Warfarin | Total |
|---|---|---|---|---|
| Age, Continuous | 69.9 years STANDARD_DEVIATION 7.5 | 68.3 years STANDARD_DEVIATION 9.1 | 67.4 years STANDARD_DEVIATION 8.8 | 68.4 years STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 10 Participants | 5 Participants | 5 Participants | 20 Participants |
| Sex: Female, Male Male | 36 Participants | 53 Participants | 57 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 46 | 25 / 58 | 16 / 62 |
| serious Total, serious adverse events | 0 / 46 | 6 / 58 | 5 / 62 |
Outcome results
Primary
Changes in Laboratory Test Values
The number of patients with ALT, AST, alkaline phosphatase, or bilirubin exceeded the upper limit of normal (ULN) range
Time frame: 12 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Changes in Laboratory Test Values | ALT > 1 x ULN | 1 participants |
| Dabigatran Etexilate 220 mg Daily | Changes in Laboratory Test Values | AST > 1 x ULN | 0 participants |
| Dabigatran Etexilate 220 mg Daily | Changes in Laboratory Test Values | Alkaline phosphatase > 1 x ULN | 2 participants |
| Dabigatran Etexilate 220 mg Daily | Changes in Laboratory Test Values | Total bilirubin > 1 x ULN | 6 participants |
| Dabigatran Etexilate 300 mg Daily | Changes in Laboratory Test Values | Total bilirubin > 1 x ULN | 7 participants |
| Dabigatran Etexilate 300 mg Daily | Changes in Laboratory Test Values | ALT > 1 x ULN | 4 participants |
| Dabigatran Etexilate 300 mg Daily | Changes in Laboratory Test Values | Alkaline phosphatase > 1 x ULN | 3 participants |
| Dabigatran Etexilate 300 mg Daily | Changes in Laboratory Test Values | AST > 1 x ULN | 4 participants |
| Warfarin | Changes in Laboratory Test Values | Total bilirubin > 1 x ULN | 8 participants |
| Warfarin | Changes in Laboratory Test Values | AST > 1 x ULN | 5 participants |
| Warfarin | Changes in Laboratory Test Values | Alkaline phosphatase > 1 x ULN | 1 participants |
| Warfarin | Changes in Laboratory Test Values | ALT > 1 x ULN | 4 participants |
Primary
Discontinuation of the Study Drug Due to Adverse Events
Discontinuation of the study drug due to adverse events.
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Discontinuation of the Study Drug Due to Adverse Events | 4 participants |
| Dabigatran Etexilate 300 mg Daily | Discontinuation of the Study Drug Due to Adverse Events | 8 participants |
| Warfarin | Discontinuation of the Study Drug Due to Adverse Events | 4 participants |
Primary
Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event
The percentage of patients with clinically relevant bleeding event. Any bleed that did not qualify as a major bleed was defined as a minor bleed; minor bleed which fulfilled one of the criteria below was defined as a clinically relevant bleeding event: * A skin haematoma of at least 25 sqcm * Spontaneous nose bleed lasting for more than 5 minutes * Macroscopic haematuria (either spontaneous or, if associated with an intervention, lasting more than 24 hours) * Spontaneous rectal bleeding (more than spotting on toilet paper) * Gingival bleeding lasting for more than 5 minutes * Bleeding leading to hospitalisation * Bleeding leading to blood transfusion (erythrocyte component transfusion or whole blood transfusion) of less than 4.5 units (equal to 2 units in EU/US) * Any other bleeding considered clinically relevant by the investigator
Time frame: upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event | 4.3 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event | 8.6 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event | 8.1 Percentage of patients |
Primary
Frequency (Occurrence Rates) of Major Bleeding Event
The percentage of patients with major bleeding event. Major bleeding was defined as any bleed fulfilling one of the following conditions: * Fatal or life-threatening * Retroperitoneal, intracranial, intraocular, or intraspinal bleeding (verified by objective testing) * Bleeding requiring surgical treatment * Clinically overt bleeding leading to a transfusion (erythrocyte component transfusion or whole blood transfusion) of 4.5 units (equal to 2 units in EU/US) or more * Clinically overt bleeding leading to a fall in haemoglobin of at least 2 g/dL
Time frame: upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of Major Bleeding Event | 0 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of Major Bleeding Event | 1.7 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of Major Bleeding Event | 3.2 Percentage of patients |
Primary
Frequency (Occurrence Rates) of Nuisance Bleeding Event
The percentage of patients with nuisance bleeding event Any bleed that did not qualify as a major bleed was defined as a minor bleed; all minor bleeding events not fulfilling one of the criteria below was defined as a nuisance bleeding event: * A skin haematoma of at least 25 sqcm * Spontaneous nose bleed lasting for more than 5 minutes * Macroscopic haematuria (either spontaneous or, if associated with an intervention, lasting more than 24 hours) * Spontaneous rectal bleeding (more than spotting on toilet paper) * Gingival bleeding lasting for more than 5 minutes * Bleeding leading to hospitalisation * Bleeding leading to blood transfusion (erythrocyte component transfusion or whole blood transfusion) of less than 4.5 units (equal to 2 units in EU/US) * Any other bleeding considered clinically relevant by the investigator
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of Nuisance Bleeding Event | 19.6 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of Nuisance Bleeding Event | 29.3 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of Nuisance Bleeding Event | 19.4 Percentage of patients |
Primary
Incidence and Severity of Adverse Events
Intensity of event is categorised as mild, moderate and severe.
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Incidence and Severity of Adverse Events | Moderate | 1 participants |
| Dabigatran Etexilate 220 mg Daily | Incidence and Severity of Adverse Events | Mild | 28 participants |
| Dabigatran Etexilate 220 mg Daily | Incidence and Severity of Adverse Events | Severe | 0 participants |
| Dabigatran Etexilate 300 mg Daily | Incidence and Severity of Adverse Events | Moderate | 1 participants |
| Dabigatran Etexilate 300 mg Daily | Incidence and Severity of Adverse Events | Mild | 46 participants |
| Dabigatran Etexilate 300 mg Daily | Incidence and Severity of Adverse Events | Severe | 2 participants |
| Warfarin | Incidence and Severity of Adverse Events | Mild | 35 participants |
| Warfarin | Incidence and Severity of Adverse Events | Severe | 2 participants |
| Warfarin | Incidence and Severity of Adverse Events | Moderate | 4 participants |
Secondary
Anticoagulation Effects Trough 11-dehydrothromboxane B2
Analysis based on concomitant use of aspirin compared to no aspirin users. 11-dehydrothromboxane B2 is measured in urine of patients.
Time frame: Week 0 and 12
Population: Per Protocol Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 0 without aspirin, N=34, N=43, N=37 | 2730 pg/mg creatinine | Geometric Coefficient of Variation 80.5 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 0 with aspirin, N=9, N=12, N=20 | 1890 pg/mg creatinine | Geometric Coefficient of Variation 49.5 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 12 without aspirin, N=34, N=42, N=37 | 3350 pg/mg creatinine | Geometric Coefficient of Variation 62.8 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 12 with aspirin, N=9, N=13, N=21 | 2380 pg/mg creatinine | Geometric Coefficient of Variation 71.2 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 12 with aspirin, N=9, N=13, N=21 | 1830 pg/mg creatinine | Geometric Coefficient of Variation 30.4 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 0 without aspirin, N=34, N=43, N=37 | 3190 pg/mg creatinine | Geometric Coefficient of Variation 65.5 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 12 without aspirin, N=34, N=42, N=37 | 3430 pg/mg creatinine | Geometric Coefficient of Variation 56.5 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 0 with aspirin, N=9, N=12, N=20 | 1480 pg/mg creatinine | Geometric Coefficient of Variation 49.9 |
| Warfarin | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 12 with aspirin, N=9, N=13, N=21 | 1420 pg/mg creatinine | Geometric Coefficient of Variation 55.3 |
| Warfarin | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 0 with aspirin, N=9, N=12, N=20 | 1660 pg/mg creatinine | Geometric Coefficient of Variation 54.3 |
| Warfarin | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 12 without aspirin, N=34, N=42, N=37 | 3520 pg/mg creatinine | Geometric Coefficient of Variation 53.9 |
| Warfarin | Anticoagulation Effects Trough 11-dehydrothromboxane B2 | week 0 without aspirin, N=34, N=43, N=37 | 3080 pg/mg creatinine | Geometric Coefficient of Variation 52.3 |
Secondary
Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time)
The blood coagulation parameter aPTT was assessed in patients allocated to the dabigatran etexilate groups at week 0, prior to drug administration and at the trough at week 1, 4 and 12.
Time frame: Week 0,1,4 and 12
Population: Full Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) | week 4, N=40, N=50 | 40.9 seconds | Geometric Coefficient of Variation 16.2 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) | week 0, N=46 , N=58 | 32.4 seconds | Geometric Coefficient of Variation 12.7 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) | week 12, N=40, N=48 | 41.8 seconds | Geometric Coefficient of Variation 17.3 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) | week 1, N=41, N=55 | 40.2 seconds | Geometric Coefficient of Variation 16.4 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) | week 12, N=40, N=48 | 44.1 seconds | Geometric Coefficient of Variation 18.2 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) | week 1, N=41, N=55 | 45.0 seconds | Geometric Coefficient of Variation 20.7 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) | week 4, N=40, N=50 | 45.0 seconds | Geometric Coefficient of Variation 17.9 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) | week 0, N=46 , N=58 | 34.0 seconds | Geometric Coefficient of Variation 25 |
Secondary
Anticoagulation Effects Trough ECT (Ecarin Clotting Time)
The blood coagulation parameter ECT was assessed in patients allocated to the dabigatran etexilate groups at week 0, prior to drug administration and at the trough at week 1, 4 and 12.
Time frame: Week 0,1,4 and 12
Population: Full Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough ECT (Ecarin Clotting Time) | week 0, N=46 , N=58 | 35.6 seconds | Geometric Coefficient of Variation 9.39 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough ECT (Ecarin Clotting Time) | week 1, N=41, N=55 | 53.4 seconds | Geometric Coefficient of Variation 23.5 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough ECT (Ecarin Clotting Time) | week 4, N=40, N=50 | 51.4 seconds | Geometric Coefficient of Variation 23.1 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough ECT (Ecarin Clotting Time) | week 12, N=40, N=48 | 52.7 seconds | Geometric Coefficient of Variation 24.1 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough ECT (Ecarin Clotting Time) | week 12, N=40, N=48 | 56.9 seconds | Geometric Coefficient of Variation 28.5 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough ECT (Ecarin Clotting Time) | week 0, N=46 , N=58 | 36.3 seconds | Geometric Coefficient of Variation 10.5 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough ECT (Ecarin Clotting Time) | week 4, N=40, N=50 | 58.9 seconds | Geometric Coefficient of Variation 27.7 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough ECT (Ecarin Clotting Time) | week 1, N=41, N=55 | 63.2 seconds | Geometric Coefficient of Variation 35.3 |
Secondary
Anticoagulation Effects Trough INR (International Normalised Ratio)
The blood coagulation parameter INR was assessed in patients allocated to the dabigatran etexilate groups at week 0, prior to drug administration and at the trough at week 1, 4 and 12.
Time frame: Week 0,1,4 and 12
Population: Full Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough INR (International Normalised Ratio) | week 0, N=46 , N=58 | 1.87 ratio | Geometric Coefficient of Variation 35.7 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough INR (International Normalised Ratio) | week 1, N=41, N=55 | 1.35 ratio | Geometric Coefficient of Variation 14 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough INR (International Normalised Ratio) | week 4, N=40, N=50 | 1.35 ratio | Geometric Coefficient of Variation 16.6 |
| Dabigatran Etexilate 220 mg Daily | Anticoagulation Effects Trough INR (International Normalised Ratio) | week 12, N=39, N=49 | 1.43 ratio | Geometric Coefficient of Variation 21.2 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough INR (International Normalised Ratio) | week 12, N=39, N=49 | 1.49 ratio | Geometric Coefficient of Variation 25.2 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough INR (International Normalised Ratio) | week 0, N=46 , N=58 | 2.03 ratio | Geometric Coefficient of Variation 33.4 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough INR (International Normalised Ratio) | week 4, N=40, N=50 | 1.46 ratio | Geometric Coefficient of Variation 18 |
| Dabigatran Etexilate 300 mg Daily | Anticoagulation Effects Trough INR (International Normalised Ratio) | week 1, N=41, N=55 | 1.49 ratio | Geometric Coefficient of Variation 20 |
Secondary
Frequency (Occurrence Rates) of a Composite Clinical Endpoint.
Percentage of patients with the composite clinical endpoint (ischemic or haemorrhagic stroke (fatal or non-fatal), transient ischemic attacks, systemic embolism, myocardial infarction (fatal or non-fatal), other major adverse cardiac events, and death)
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of a Composite Clinical Endpoint. | 0 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of a Composite Clinical Endpoint. | 0 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of a Composite Clinical Endpoint. | 1.6 Percentage of patients |
Secondary
Frequency (Occurrence Rates) of Death
The percentage of patients with death
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of Death | 0 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of Death | 0 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of Death | 0 Percentage of patients |
Secondary
Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal)
The percentage of patients with ischemic or haemorrhagic stroke (fatal or non-fatal)
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal) | 0 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal) | 0 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal) | 1.6 Percentage of patients |
Secondary
Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal)
The percentage of patients with myocardial infarction (fatal or non-fatal)
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal) | 0 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal) | 0 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal) | 0 Percentage of patients |
Secondary
Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events
The percentage of patients with other major adverse cardiac events
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events | 0 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events | 0 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events | 0 Percentage of patients |
Secondary
Frequency (Occurrence Rates) of Systemic Embolism
The percentage of patients with systemic embolism
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of Systemic Embolism | 0 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of Systemic Embolism | 0 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of Systemic Embolism | 0 Percentage of patients |
Secondary
Frequency (Occurrence Rates) of Transient Ischemic Attack
The percentage of patients with transient ischemic attack
Time frame: Upto 15 weeks
Population: Safety set was used for safety endpoints. Full analysis set was used for efficacy endpoints. The safety set comprises all patients who were treated with trial medication at least once. The full analysis set comprises all patients who were randomised and treated with trial medication at least once. No data was imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Frequency (Occurrence Rates) of Transient Ischemic Attack | 0 Percentage of patients |
| Dabigatran Etexilate 300 mg Daily | Frequency (Occurrence Rates) of Transient Ischemic Attack | 0 Percentage of patients |
| Warfarin | Frequency (Occurrence Rates) of Transient Ischemic Attack | 0 Percentage of patients |
Secondary
Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration
Time frame: Week 1,4 and 12
Population: Full Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dabigatran Etexilate 220 mg Daily | Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration | week 1, N=41, N=55 | 53.1 ng/mL | Geometric Coefficient of Variation 69 |
| Dabigatran Etexilate 220 mg Daily | Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration | week 4, N=40, N=50 | 55.6 ng/mL | Geometric Coefficient of Variation 62.5 |
| Dabigatran Etexilate 220 mg Daily | Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration | week 12, N=39, N=49 | 63.0 ng/mL | Geometric Coefficient of Variation 62.1 |
| Dabigatran Etexilate 300 mg Daily | Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration | week 1, N=41, N=55 | 78.1 ng/mL | Geometric Coefficient of Variation 75.8 |
| Dabigatran Etexilate 300 mg Daily | Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration | week 4, N=40, N=50 | 78.2 ng/mL | Geometric Coefficient of Variation 68.1 |
| Dabigatran Etexilate 300 mg Daily | Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration | week 12, N=39, N=49 | 75.1 ng/mL | Geometric Coefficient of Variation 63.3 |