Trial Outcomes & Findings for Phase III Study Testing Efficacy & Safety of Oral Dabigatran Etexilate vs Warfarin for 6 m Treatment for Acute Symp Venous Thromboembolism (VTE) (NCT NCT00680186)

Last Updated: 2014-05-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2589 participants

Primary outcome timeframe

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)

Results posted on

2014-05-19

Participant Flow

There were 2589 patients enrolled/randomised but only 2568 were treated.

Participant milestones

Participant milestones
Measure	Dabigatran 150 mg bid (twice daily) oral	Warfarin PRN (as needed) to maintain an INR (international normalised ratio) of 2.0-3.0
Overall Study STARTED	1280	1288
Overall Study COMPLETED	1155	1172
Overall Study NOT COMPLETED	125	116

Reasons for withdrawal

Reasons for withdrawal
Measure	Dabigatran 150 mg bid (twice daily) oral	Warfarin PRN (as needed) to maintain an INR (international normalised ratio) of 2.0-3.0
Overall Study Adverse Event	47	44
Overall Study Protocol Violation	31	26
Overall Study Lost to Follow-up	11	6
Overall Study Withdrawal by Subject	32	39
Overall Study Other	4	1

Baseline Characteristics

Phase III Study Testing Efficacy & Safety of Oral Dabigatran Etexilate vs Warfarin for 6 m Treatment for Acute Symp Venous Thromboembolism (VTE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dabigatran 150 mg n=1280 Participants bid oral	Warfarin n=1288 Participants PRN to maintain an INR of 2.0-3.0	Total n=2568 Participants Total of all reporting groups
Age, Continuous	54.7 Years STANDARD_DEVIATION 16.19 • n=5 Participants	55.1 Years STANDARD_DEVIATION 16.26 • n=7 Participants	54.9 Years STANDARD_DEVIATION 16.22 • n=5 Participants
Sex: Female, Male Female	499 Participants n=5 Participants	512 Participants n=7 Participants	1011 Participants n=5 Participants
Sex: Female, Male Male	781 Participants n=5 Participants	776 Participants n=7 Participants	1557 Participants n=5 Participants
Investigator assessed acute symptomatic deep vein thrombosis (DVT) of leg or pulmonary embolism (PE) Symptomatic PE and symptomatic DVT	104 participants n=5 Participants	117 participants n=7 Participants	221 participants n=5 Participants
Investigator assessed acute symptomatic deep vein thrombosis (DVT) of leg or pulmonary embolism (PE) Symptomatic PE	298 participants n=5 Participants	297 participants n=7 Participants	595 participants n=5 Participants
Investigator assessed acute symptomatic deep vein thrombosis (DVT) of leg or pulmonary embolism (PE) Symptomatic DVT	877 participants n=5 Participants	873 participants n=7 Participants	1750 participants n=5 Participants
Investigator assessed acute symptomatic deep vein thrombosis (DVT) of leg or pulmonary embolism (PE) No PE and no DVT	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants

PRIMARY outcome

Timeframe: 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)

Population: 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.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1279 Participants bid oral	Warfarin n=1289 Participants PRN to maintain an INR of 2.0-3.0
Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE Participants with event (up to day 180)	30 participants	28 participants
Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE Participants with event (up to end of ptp)	34 participants	30 participants

SECONDARY outcome

Timeframe: 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.

Population: FAS

VTE or any death which occured from randomisation to end of ptp. 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.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1279 Participants bid oral	Warfarin n=1289 Participants PRN to maintain an INR of 2.0-3.0
Number of Participants With Recurrent Symptomatic VTE and All Deaths Participants with event (up to day 180)	51 participants	48 participants
Number of Participants With Recurrent Symptomatic VTE and All Deaths Participants with event (up to end of ptp)	57 participants	51 participants

SECONDARY outcome

Timeframe: 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.

Population: FAS

Symptomatic DVT which occured from randomisation to end of ptp. 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.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1279 Participants bid oral	Warfarin n=1289 Participants PRN to maintain an INR of 2.0-3.0
Number of Participants With Recurrent Symptomatic DVT Participants with event (up to day 180)	25 participants	17 participants
Number of Participants With Recurrent Symptomatic DVT Participants with event (up to end of ptp)	28 participants	17 participants

SECONDARY outcome

Timeframe: 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.

Population: FAS

Symptomatic non-fatal PE which occured from randomisation to end of ptp. 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.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1279 Participants bid oral	Warfarin n=1289 Participants PRN to maintain an INR of 2.0-3.0
Number of Participants With Recurrent Symptomatic Non-fatal PE Participants with event (up to day 180)	7 participants	13 participants
Number of Participants With Recurrent Symptomatic Non-fatal PE Participants with event (up to end of ptp)	9 participants	15 participants

SECONDARY outcome

Timeframe: From randomisation to 6 months (up to day 180) and to end of ptp (planned to be up to day 224)

Population: FAS

VTE - related deaths which occured from randomisation to end of ptp. 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. Hazard ratios and 95% CI were not calculated because of insufficient number of events.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1279 Participants bid oral	Warfarin n=1289 Participants PRN to maintain an INR of 2.0-3.0
Number of Participants Who Died Due to VTE Participants with event (up to day 180)	3 participants	0 participants
Number of Participants Who Died Due to VTE Participants with event (up to end of ptp)	3 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Population: FAS

Any deaths which occured from randomisation to end of ptp. 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.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1279 Participants bid oral	Warfarin n=1289 Participants PRN to maintain an INR of 2.0-3.0
Number of Participants Who Died (Any Cause) Participants with event (up to day 180)	25 participants	25 participants
Number of Participants Who Died (Any Cause) Participants with event (up to end of ptp)	29 participants	26 participants

SECONDARY outcome

Timeframe: 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.

Population: FAS

Symptomatic fatal and non-fatal PE which occured from randomisation to end of ptp. 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.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1279 Participants bid oral	Warfarin n=1289 Participants PRN to maintain an INR of 2.0-3.0
Number of Participants With Recurrent Symptomatic Fatal and Non-fatal PE Participants with event (up to end of ptp)	10 participants	15 participants
Number of Participants With Recurrent Symptomatic Fatal and Non-fatal PE Participants with event (up to day 180)	8 participants	13 participants

SECONDARY outcome

Timeframe: From first intake of study drug to last intake of study drug + 6 days washout

Population: 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.

Major bleeding events (MBE) are 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) are defined as * spontaneous skin hematoma \>=25 cm² * wound hematoma \>=100 cm² * spontaneous nose bleed \>5 min * macroscopic hematuria spontaneous or \>24 hours if associated with an intervention * spontaneous rectal bleeding * 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.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1280 Participants bid oral	Warfarin n=1288 Participants PRN to maintain an INR of 2.0-3.0
Number of Participants With MBE, MBE and/or CRBE, and Any Bleeding Events MBE	15 participants	22 participants
Number of Participants With MBE, MBE and/or CRBE, and Any Bleeding Events MBE and/or CRBE	64 participants	102 participants
Number of Participants With MBE, MBE and/or CRBE, and Any Bleeding Events Any bleeding event	200 participants	285 participants

SECONDARY outcome

Timeframe: From first intake of study drug to last contact date

Population: TS

Any ACS occurring during the conduct of the study (centrally adjudicated as definite). Patients having a centrally adjudicated definite ACS during intake of study drug and after stopping study drug, according to treatment group. ACS assessments pre-specified in the protocol without adjudication. Prior to database lock, the steering committee asked to have ACS events adjudicated by an independent committee. After database lock, the committee was provided with source documentation that was blinded to the patient's treatment assignment. ACS results presented are based on adjudication findings.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1280 Participants bid oral	Warfarin n=1288 Participants PRN to maintain an INR of 2.0-3.0
Number of Participants With Acute Coronary Syndrome (ACS) After stopping study drug	2 participants	1 participants
Number of Participants With Acute Coronary Syndrome (ACS) During intake of study drug	3 participants	0 participants

SECONDARY outcome

Timeframe: From first intake of study drug to last intake of study drug + 6 days washout

Population: TS

Frequency of patients with possible clinically significant abnormalities.

Outcome measures

Outcome measures
Measure	Dabigatran 150 mg n=1238 Participants bid oral	Warfarin n=1248 Participants PRN to maintain an INR of 2.0-3.0
Laboratory Analyses Bilirubin decrease	0 participants	0 participants
Laboratory Analyses AST increase	29 participants	27 participants
Laboratory Analyses AST decrease	0 participants	0 participants
Laboratory Analyses ALT increase	31 participants	40 participants
Laboratory Analyses ALT decrease	0 participants	0 participants
Laboratory Analyses Bilirubin increase	8 participants	6 participants

Adverse Events

Dabigatran 150 mg

Serious events: 156 serious events

Other events: 124 other events

Deaths: 0 deaths

Warfarin

Serious events: 153 serious events

Other events: 126 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Dabigatran 150 mg n=1280 participants at risk bid oral	Warfarin n=1288 participants at risk PRN to maintain an INR of 2.0-3.0
Musculoskeletal and connective tissue disorders Pain in extremity	5.9% 75/1280 • From first intake of study drug to last intake of study drug + 6 days washout	5.4% 69/1288 • From first intake of study drug to last intake of study drug + 6 days washout
Nervous system disorders Headache	4.5% 57/1280 • From first intake of study drug to last intake of study drug + 6 days washout	5.4% 70/1288 • From first intake of study drug to last intake of study drug + 6 days washout

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

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