Trial Outcomes & Findings for Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long Term Prevention of Recurrent Symptomatic VTE (NCT NCT00558259)

Last Updated: 2014-06-27

Results Overview

Symptomatic recurrent VTE is the composite of recurrent deep vein thrombosis (DVT) , fatal or non-fatal pulmonary embolism (PE). Whilst the endpoint is time to event, the measured values present the number of participant with event and the hazard ratio presents the time to event.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1353 participants

Primary outcome timeframe

6 months

Results posted on

2014-06-27

Participant Flow

There were 3 patients randomised to placebo who received Dabigatran only. For all analyses of efficacy, these patients are analysed as randomised. For all analyses of safety, these patients are analysed as treated.

Participant milestones

Participant milestones
Measure	Dabigatran Dabigatran 150mg bid (twice daily)	Placebo Matching placebo
Overall Study STARTED	681	662
Overall Study COMPLETED	610	563
Overall Study NOT COMPLETED	71	99

Reasons for withdrawal

Reasons for withdrawal
Measure	Dabigatran Dabigatran 150mg bid (twice daily)	Placebo Matching placebo
Overall Study Adverse Event	50	81
Overall Study Protocol Violation	9	5
Overall Study Withdrawal by Subject	12	13

Baseline Characteristics

Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long Term Prevention of Recurrent Symptomatic VTE

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dabigatran n=681 Participants Dabigatran 150mg bid	Placebo n=662 Participants Matching placebo	Total n=1343 Participants Total of all reporting groups
Age, Continuous	56.1 Years STANDARD_DEVIATION 15.5 • n=5 Participants	55.5 Years STANDARD_DEVIATION 15.1 • n=7 Participants	55.8 Years STANDARD_DEVIATION 15.3 • n=5 Participants
Sex: Female, Male Female	300 Participants n=5 Participants	298 Participants n=7 Participants	598 Participants n=5 Participants
Sex: Female, Male Male	381 Participants n=5 Participants	364 Participants n=7 Participants	745 Participants n=5 Participants
Body mass index (BMI) continuous	28.45 kg/m^2 STANDARD_DEVIATION 5.44 • n=5 Participants	28.41 kg/m^2 STANDARD_DEVIATION 5.56 • n=7 Participants	28.43 kg/m^2 STANDARD_DEVIATION 5.50 • n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Full analysis set (FAS) and analysed as randomised. FAS is defined as randomised and treated.

Outcome measures

Outcome measures
Measure	Dabigatran n=681 Participants Dabigatran 150mg bid	Placebo n=662 Participants Matching placebo
Centrally Confirmed Symptomatic Recurrent Venous Thrombotic Events (VTE) Including Unexplained Death During the Intended Treatment Period	3 Participants 0.0	37 Participants 0.0

SECONDARY outcome

Timeframe: 6 months

Population: FAS and analysed as randomised.

Outcome measures

Outcome measures
Measure	Dabigatran n=681 Participants Dabigatran 150mg bid	Placebo n=662 Participants Matching placebo
Centrally Confirmed Symptomatic Recurrent Venous Thrombotic Events (VTE) Excluding Unexplained Death During the Intended Treatment Period	3 Participants	35 Participants

SECONDARY outcome

Timeframe: 6 months

Population: FAS and analysed as randomised.

Number of the participants with centrally confirmed symptomatic recurrent deep venous thrombotic (DVT) events during the intended treatment period were described.

Outcome measures

Outcome measures
Measure	Dabigatran n=681 Participants Dabigatran 150mg bid	Placebo n=662 Participants Matching placebo
Centrally Confirmed Symptomatic Recurrent Deep Venous Thrombotic (DVT) Events During the Intended Treatment Period	2 Participants	23 Participants

SECONDARY outcome

Timeframe: 6 months

Population: FAS and analysed as randomised.

Number of participants with centrally confirmed symptomatic pulmonary embolism (PE) events during the intended treatment period were described.

Outcome measures

Outcome measures
Measure	Dabigatran n=681 Participants Dabigatran 150mg bid	Placebo n=662 Participants Matching placebo
Centrally Confirmed Symptomatic Pulmonary Embolism (PE) Events During the Intended Treatment Period	1 Participants	14 Participants

SECONDARY outcome

Timeframe: 6 months

Population: FAS and analysed as randomised.

Number of participants with centrally confirmed unexplained deaths during the intended treatment period were described.

Outcome measures

Outcome measures
Measure	Dabigatran n=681 Participants Dabigatran 150mg bid	Placebo n=662 Participants Matching placebo
Centrally Confirmed Unexplained Deaths During the Intended Treatment Period	0 participants	2 participants

SECONDARY outcome

Timeframe: 6 months

Population: FAS and analysed as treated. There were 3 participants who were randomised to placebo but treated with dabigatran only.

Major bleeding events (MBE) had to fulfil at least 1 of the following criteria: * Fatal bleeding * Associated with a fall in haemoglobin of ≥2 g/dL * Led to the transfusion of ≥2 units packed cells or whole blood * Occurred in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal Other clinically relevant bleeding was defined as overt bleeding not meeting the criteria for an MBE but associated with medical intervention, unscheduled contact with a physician, (temporary) cessation of study treatment, or associated with discomfort such as pain, or impairment of activities of daily life. Examples of these bleedings were: * Bleeding that compromised haemodynamics * Bleeding that led to hospitalisation Trivial bleeding events were defined as all other bleeding events that did not fulfil the criteria of MBEs or CRBEs. All bleeding events include MBEs, CRBEs, and trivial bleeding events.

Outcome measures

Outcome measures
Measure	Dabigatran n=684 Participants Dabigatran 150mg bid	Placebo n=659 Participants Matching placebo
Centrally Confirmed Bleeding Event During the Treatment Period MBE	2 participants	0 participants
Centrally Confirmed Bleeding Event During the Treatment Period MBE or CRBE	36 participants	12 participants
Centrally Confirmed Bleeding Event During the Treatment Period All Bleeding	72 participants	39 participants

SECONDARY outcome

Timeframe: 6 months

Population: FAS and analysed as treated. There were 3 participants who were randomised to placebo but treated with dabigatran only.

Cardiovascular events that occurred during the treatment period + 3 days were summarised by treatment groups.

Outcome measures

Outcome measures
Measure	Dabigatran n=684 Participants Dabigatran 150mg bid	Placebo n=659 Participants Matching placebo
Centrally Confirmed Cardiovascular Events During the Treatment Period	3 participants	2 participants

SECONDARY outcome

Timeframe: 6 months

Population: FAS - As Treated Assignment

Number of participants with possible clinically significant abnormalities during the treatment period.

Outcome measures

Outcome measures
Measure	Dabigatran n=684 Participants Dabigatran 150mg bid	Placebo n=659 Participants Matching placebo
Laboratory Measures, Especially Liver Function Tests (LFTs) AST increase (N=655, 629)	2 participants	2 participants
Laboratory Measures, Especially Liver Function Tests (LFTs) ALT increase (N=655, 629)	3 participants	5 participants
Laboratory Measures, Especially Liver Function Tests (LFTs) Alkaline phosphatase increase (N=658, 629)	0 participants	0 participants
Laboratory Measures, Especially Liver Function Tests (LFTs) Total bilirubin increase (N=658, 628)	1 participants	1 participants

Adverse Events

Dabigatran

Serious events: 47 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 60 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

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