Trial Outcomes & Findings for A Dose Response Study of Dabigatran Etexilate(BIBR 1048) in Pharmacodynamics and Safety in Patients With Non-valvular Atrial Fibrillation in Comparison to Warfarin (NCT NCT01136408)

NCT ID: NCT01136408

Last Updated: 2014-03-19

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 174 participants
• Primary outcome timeframe: upto 15 weeks
• Results posted on: 2014-03-19

Participant Flow

Eight patients were randomised but not treated with study drug, hence resulting in 174 patients as enrolled and 166 who were actually treated.

Participant milestones

Measure	Dabigatran Etexilate 220 mg Daily Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin Dose-adjusted warfarin based on target INR values
Overall Study STARTED	46	58	62
Overall Study COMPLETED	41	49	57
Overall Study NOT COMPLETED	5	9	5

Reasons for withdrawal

Measure	Dabigatran Etexilate 220 mg Daily Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin Dose-adjusted warfarin based on target INR values
Overall Study Adverse Event	4	8	4
Overall Study Protocol Violation	1	1	1

Baseline Characteristics

A Dose Response Study of Dabigatran Etexilate(BIBR 1048) in Pharmacodynamics and Safety in Patients With Non-valvular Atrial Fibrillation in Comparison to Warfarin

Baseline characteristics by cohort

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values	Total n=166 Participants Total of all reporting groups
Age, Continuous	69.9 years STANDARD_DEVIATION 7.5 • n=5 Participants	68.3 years STANDARD_DEVIATION 9.1 • n=7 Participants	67.4 years STANDARD_DEVIATION 8.8 • n=5 Participants	68.4 years STANDARD_DEVIATION 8.6 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	20 Participants n=4 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	53 Participants n=7 Participants	57 Participants n=5 Participants	146 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of Major Bleeding Event	0 Percentage of patients	1.7 Percentage of patients	3.2 Percentage of patients

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of Clinically Relevant Bleeding Event	4.3 Percentage of patients	8.6 Percentage of patients	8.1 Percentage of patients

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of Nuisance Bleeding Event	19.6 Percentage of patients	29.3 Percentage of patients	19.4 Percentage of patients

PRIMARY outcome

Timeframe: 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.

Intensity of event is categorised as mild, moderate and severe.

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Incidence and Severity of Adverse Events Mild	28 participants	46 participants	35 participants
Incidence and Severity of Adverse Events Moderate	1 participants	1 participants	4 participants
Incidence and Severity of Adverse Events Severe	0 participants	2 participants	2 participants

PRIMARY outcome

Timeframe: 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.

Discontinuation of the study drug due to adverse events.

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Discontinuation of the Study Drug Due to Adverse Events	4 participants	8 participants	4 participants

PRIMARY outcome

Timeframe: 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.

The number of patients with ALT, AST, alkaline phosphatase, or bilirubin exceeded the upper limit of normal (ULN) range

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=60 Participants Dose-adjusted warfarin based on target INR values
Changes in Laboratory Test Values ALT > 1 x ULN	1 participants	4 participants	4 participants
Changes in Laboratory Test Values AST > 1 x ULN	0 participants	4 participants	5 participants
Changes in Laboratory Test Values Alkaline phosphatase > 1 x ULN	2 participants	3 participants	1 participants
Changes in Laboratory Test Values Total bilirubin > 1 x ULN	6 participants	7 participants	8 participants

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of a Composite Clinical Endpoint.	0 Percentage of patients	0 Percentage of patients	1.6 Percentage of patients

SECONDARY outcome

Timeframe: 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.

The percentage of patients with ischemic or haemorrhagic stroke (fatal or non-fatal)

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of Ischemic or Haemorrhagic Stroke (Fatal or Non-fatal)	0 Percentage of patients	0 Percentage of patients	1.6 Percentage of patients

SECONDARY outcome

Timeframe: 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.

The percentage of patients with transient ischemic attack

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of Transient Ischemic Attack	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients

SECONDARY outcome

Timeframe: 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.

The percentage of patients with systemic embolism

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of Systemic Embolism	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients

SECONDARY outcome

Timeframe: 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.

The percentage of patients with myocardial infarction (fatal or non-fatal)

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of Myocardial Infarction (Fatal or Non-fatal)	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients

SECONDARY outcome

Timeframe: 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.

The percentage of patients with other major adverse cardiac events

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of Other Major Adverse Cardiac Events	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients

SECONDARY outcome

Timeframe: 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.

The percentage of patients with death

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 Participants Dose-adjusted warfarin based on target INR values
Frequency (Occurrence Rates) of Death	0 Percentage of patients	0 Percentage of patients	0 Percentage of patients

SECONDARY outcome

Timeframe: Week 0,1,4 and 12

Population: Full Analysis Set

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.

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin Dose-adjusted warfarin based on target INR values
Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) week 0, N=46 , N=58	32.4 seconds Geometric Coefficient of Variation 12.7	34.0 seconds Geometric Coefficient of Variation 25.0	—
Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) week 1, N=41, N=55	40.2 seconds Geometric Coefficient of Variation 16.4	45.0 seconds Geometric Coefficient of Variation 20.7	—
Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) week 4, N=40, N=50	40.9 seconds Geometric Coefficient of Variation 16.2	45.0 seconds Geometric Coefficient of Variation 17.9	—
Anticoagulation Effects Trough aPTT (Activated Partial Thromboplastin Time) week 12, N=40, N=48	41.8 seconds Geometric Coefficient of Variation 17.3	44.1 seconds Geometric Coefficient of Variation 18.2	—

SECONDARY outcome

Timeframe: Week 0,1,4 and 12

Population: Full Analysis Set

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.

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin Dose-adjusted warfarin based on target INR values
Anticoagulation Effects Trough ECT (Ecarin Clotting Time) week 0, N=46 , N=58	35.6 seconds Geometric Coefficient of Variation 9.39	36.3 seconds Geometric Coefficient of Variation 10.5	—
Anticoagulation Effects Trough ECT (Ecarin Clotting Time) week 1, N=41, N=55	53.4 seconds Geometric Coefficient of Variation 23.5	63.2 seconds Geometric Coefficient of Variation 35.3	—
Anticoagulation Effects Trough ECT (Ecarin Clotting Time) week 4, N=40, N=50	51.4 seconds Geometric Coefficient of Variation 23.1	58.9 seconds Geometric Coefficient of Variation 27.7	—
Anticoagulation Effects Trough ECT (Ecarin Clotting Time) week 12, N=40, N=48	52.7 seconds Geometric Coefficient of Variation 24.1	56.9 seconds Geometric Coefficient of Variation 28.5	—

SECONDARY outcome

Timeframe: Week 0,1,4 and 12

Population: Full Analysis Set

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.

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin Dose-adjusted warfarin based on target INR values
Anticoagulation Effects Trough INR (International Normalised Ratio) week 0, N=46 , N=58	1.87 ratio Geometric Coefficient of Variation 35.7	2.03 ratio Geometric Coefficient of Variation 33.4	—
Anticoagulation Effects Trough INR (International Normalised Ratio) week 1, N=41, N=55	1.35 ratio Geometric Coefficient of Variation 14.0	1.49 ratio Geometric Coefficient of Variation 20.0	—
Anticoagulation Effects Trough INR (International Normalised Ratio) week 4, N=40, N=50	1.35 ratio Geometric Coefficient of Variation 16.6	1.46 ratio Geometric Coefficient of Variation 18.0	—
Anticoagulation Effects Trough INR (International Normalised Ratio) week 12, N=39, N=49	1.43 ratio Geometric Coefficient of Variation 21.2	1.49 ratio Geometric Coefficient of Variation 25.2	—

SECONDARY outcome

Timeframe: Week 0 and 12

Population: Per Protocol Analysis Set

Analysis based on concomitant use of aspirin compared to no aspirin users. 11-dehydrothromboxane B2 is measured in urine of patients.

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=43 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=56 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=58 Participants Dose-adjusted warfarin based on target INR values
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	1480 pg/mg creatinine Geometric Coefficient of Variation 49.9	1660 pg/mg creatinine Geometric Coefficient of Variation 54.3
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	3190 pg/mg creatinine Geometric Coefficient of Variation 65.5	3080 pg/mg creatinine Geometric Coefficient of Variation 52.3
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	3430 pg/mg creatinine Geometric Coefficient of Variation 56.5	3520 pg/mg creatinine Geometric Coefficient of Variation 53.9
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	1830 pg/mg creatinine Geometric Coefficient of Variation 30.4	1420 pg/mg creatinine Geometric Coefficient of Variation 55.3

SECONDARY outcome

Timeframe: Week 1,4 and 12

Population: Full Analysis Set

Outcome measures

Measure	Dabigatran Etexilate 220 mg Daily n=46 Participants Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 Participants Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin Dose-adjusted warfarin based on target INR values
Steady-state Pharmacokinetics of Total Dabigatran Trough Plasma Concentration week 1, N=41, N=55	53.1 ng/mL Geometric Coefficient of Variation 69.0	78.1 ng/mL Geometric Coefficient of Variation 75.8	—
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	78.2 ng/mL Geometric Coefficient of Variation 68.1	—
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	75.1 ng/mL Geometric Coefficient of Variation 63.3	—

Adverse Events

Dabigatran Etexilate 220 mg Daily

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Dabigatran Etexilate 300 mg Daily

Serious events: 6 serious events

Other events: 25 other events

Deaths: 0 deaths

Warfarin

Serious events: 5 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dabigatran Etexilate 220 mg Daily n=46 participants at risk Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 participants at risk Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 participants at risk Dose-adjusted warfarin based on target INR values
Infections and infestations Pneumonia	0.00% 0/46 • First administration to end of study	1.7% 1/58 • First administration to end of study	1.6% 1/62 • First administration to end of study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/46 • First administration to end of study	1.7% 1/58 • First administration to end of study	0.00% 0/62 • First administration to end of study
Nervous system disorders Dizziness	0.00% 0/46 • First administration to end of study	0.00% 0/58 • First administration to end of study	1.6% 1/62 • First administration to end of study
Nervous system disorders Haemorrhagic cerebral infarction	0.00% 0/46 • First administration to end of study	0.00% 0/58 • First administration to end of study	1.6% 1/62 • First administration to end of study
Cardiac disorders Atrioventricular block third degree	0.00% 0/46 • First administration to end of study	1.7% 1/58 • First administration to end of study	0.00% 0/62 • First administration to end of study
Cardiac disorders Cardiac arrest	0.00% 0/46 • First administration to end of study	1.7% 1/58 • First administration to end of study	0.00% 0/62 • First administration to end of study
Cardiac disorders Cardiac failure	0.00% 0/46 • First administration to end of study	1.7% 1/58 • First administration to end of study	0.00% 0/62 • First administration to end of study
Cardiac disorders Cardiac failure congestive	0.00% 0/46 • First administration to end of study	1.7% 1/58 • First administration to end of study	0.00% 0/62 • First administration to end of study
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/46 • First administration to end of study	0.00% 0/58 • First administration to end of study	1.6% 1/62 • First administration to end of study
Gastrointestinal disorders Toothache	0.00% 0/46 • First administration to end of study	0.00% 0/58 • First administration to end of study	1.6% 1/62 • First administration to end of study
Musculoskeletal and connective tissue disorders Muscle fatigue	0.00% 0/46 • First administration to end of study	1.7% 1/58 • First administration to end of study	0.00% 0/62 • First administration to end of study
Reproductive system and breast disorders Prostatic haemorrhage	0.00% 0/46 • First administration to end of study	1.7% 1/58 • First administration to end of study	0.00% 0/62 • First administration to end of study
Injury, poisoning and procedural complications Femur fracture	0.00% 0/46 • First administration to end of study	0.00% 0/58 • First administration to end of study	1.6% 1/62 • First administration to end of study
Injury, poisoning and procedural complications Laryngeal injury	0.00% 0/46 • First administration to end of study	0.00% 0/58 • First administration to end of study	1.6% 1/62 • First administration to end of study

Other adverse events

Measure	Dabigatran Etexilate 220 mg Daily n=46 participants at risk Dabigatran etexilate 110 mg capsule, twice a day, oral administration	Dabigatran Etexilate 300 mg Daily n=58 participants at risk Dabigatran etexilate 150 mg capsule, twice a day, oral administration	Warfarin n=62 participants at risk Dose-adjusted warfarin based on target INR values
Infections and infestations Nasopharyngitis	10.9% 5/46 • First administration to end of study	17.2% 10/58 • First administration to end of study	12.9% 8/62 • First administration to end of study
Psychiatric disorders Insomnia	2.2% 1/46 • First administration to end of study	5.2% 3/58 • First administration to end of study	0.00% 0/62 • First administration to end of study
Respiratory, thoracic and mediastinal disorders Epistaxis	4.3% 2/46 • First administration to end of study	8.6% 5/58 • First administration to end of study	4.8% 3/62 • First administration to end of study
Gastrointestinal disorders Diarrhoea	2.2% 1/46 • First administration to end of study	6.9% 4/58 • First administration to end of study	3.2% 2/62 • First administration to end of study
Gastrointestinal disorders Abdominal pain upper	0.00% 0/46 • First administration to end of study	5.2% 3/58 • First administration to end of study	0.00% 0/62 • First administration to end of study
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	2.2% 1/46 • First administration to end of study	12.1% 7/58 • First administration to end of study	4.8% 3/62 • First administration to end of study

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any publication of the result 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
• Publication restrictions are in place

Restriction type: OTHER