Trial Outcomes & Findings for Dabigatran Etexilate Compared With Enoxaparin in Prevention of Venous Thromboembolism (VTE) Following Total Hip Arthroplasty (NCT NCT00657150)

Last Updated: 2014-07-02

Results Overview

Total Venous Thromboembolic Event (VTE) includes both proximal and distal deep vein thrombosis (DVT) (detected by routine venography), symptomatic DVT (confirmed by venous duplex, ultrasound, venography or autopsy) and pulmonary embolism (PE) (confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy). All of these components and all deaths were centrally adjudicated by the VTE events committee, which was not aware of the treatment allocation of the patients.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2055 participants

Primary outcome timeframe

28-35 days

Results posted on

2014-07-02

Participant Flow

The treatment period is from first administration of study medication, until 3 days after last administration of study medication. Treatment duration is planned for 28 - 35 days. The study period is from first administration of study medication until day 84 - 91.

Whilst 2055 patients were randomised to treatment prior to surgery in this trial, only 2013 started treatment. Therefore, 42 patients were randomised but not treated.

Participant milestones

Participant milestones
Measure	Dabigatran 220mg qd (once daily) oral	Enoxaparin 40mg qd (once daily) subcutaneous
Overall Study STARTED	1010	1003
Overall Study COMPLETED	895	910
Overall Study NOT COMPLETED	115	93
Treatment STARTED	1010	1003
Treatment COMPLETED	903	906
Treatment NOT COMPLETED	107	97

Reasons for withdrawal

Reasons for withdrawal
Measure	Dabigatran 220mg qd (once daily) oral	Enoxaparin 40mg qd (once daily) subcutaneous
Overall Study Adverse Event	19	10
Overall Study Non-compliant with protocol	5	9
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	51	36
Overall Study Other	38	38
Treatment Adverse Event	60	53
Treatment Non-compliant with protocol	10	9
Treatment Lost to Follow-up	1	0
Treatment Withdrawal by Subject	23	20
Treatment Other	13	15

Baseline Characteristics

Dabigatran Etexilate Compared With Enoxaparin in Prevention of Venous Thromboembolism (VTE) Following Total Hip Arthroplasty

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dabigatran 220mg n=1010 Participants qd (once daily) oral	Enoxaparin n=1003 Participants 40mg qd (once daily) subcutaneous	Total n=2013 Participants Total of all reporting groups
Age, Continuous	61.9 Years STANDARD_DEVIATION 11.5 • n=5 Participants	62.0 Years STANDARD_DEVIATION 11.3 • n=7 Participants	62.0 Years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	541 Participants n=5 Participants	501 Participants n=7 Participants	1042 Participants n=5 Participants
Sex: Female, Male Male	469 Participants n=5 Participants	502 Participants n=7 Participants	971 Participants n=5 Participants
Body Mass Index N=(1003;992;1995)	27.8 kg/m^2 STANDARD_DEVIATION 4.8 • n=5 Participants	27.8 kg/m^2 STANDARD_DEVIATION 4.8 • n=7 Participants	27.8 kg/m^2 STANDARD_DEVIATION 4.8 • n=5 Participants

PRIMARY outcome

Timeframe: 28-35 days

Population: Full Analysis Set (randomised, had taken at least 1 dose of oral or subcutaneous trial medication, had undergone surgery, had evaluable negative venogram for both distal and proximal DVT in both legs or positive venography in any 1 segment of 1 or both legs, or confirmed symptomatic DVT, PE or death during the treatment period.)

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=792 Participants qd (once daily) oral	Enoxaparin n=786 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period	61 Participants	69 Participants

SECONDARY outcome

Timeframe: 28-35 days

Population: Full Analysis Set-major (randomised, had taken at least 1 dose of oral or subcutaneous trial medication, had undergone surgery, had evaluable negative venogram for proximal DVT in both legs or a positive venogram for proximal DVT in either leg or confirmed symptomatic proximal DVT, PE or death related to VTE during the treatment period.)

Major Venous Thromboembolic Event (VTE) is defined as proximal DVT and PE, as adjudicated by the VTE events committee

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=805 Participants qd (once daily) oral	Enoxaparin n=795 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period	18 Participants	33 Participants

SECONDARY outcome

Timeframe: 28-35 days

Population: Full Analysis Set - pDVT (all patients who had been randomised, had taken at least 1 dose of oral or subcutaneous trial medication, had undergone surgery (i.e. a date of surgery was reported), evaluable negative venogram for proximal DVT in both legs or positive venogram in either leg or confirmed symptomatic proximal DVT)

Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=804 Participants qd (once daily) oral	Enoxaparin n=793 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Proximal Deep Vein Thrombosis During Treatment Period	17 Participants	31 Participants

SECONDARY outcome

Timeframe: 28-35 days

Population: Full Analysis Set-tDVT (randomised, had taken at least 1 dose of oral or subcutaneous trial medication, had undergone surgery, evaluable negative venogram for both distal and proximal DVT in both legs or positive venography in any 1 segment of 1 or both legs, or confirmed symptomatic DVT.)

Total Deep Vein Thrombosis as adjudicated by the VTE events committee

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=791 Participants qd (once daily) oral	Enoxaparin n=784 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Total Deep Vein Thrombosis During Treatment Period	60 Participants	67 Participants

SECONDARY outcome

Timeframe: 28-35 days

Population: Full Analysis Set - op (all patients who had been randomised, had taken at least 1 dose of oral or subcutaneous trial medication or had undergone surgery (i.e. a date of surgery was reported)

Symptomatic Deep Vein Thrombosis, confirmed by venous duplex, ultrasound, venography or autopsy, and as adjudicated by the VTE events committee

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=1001 Participants qd (once daily) oral	Enoxaparin n=992 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period	0 Participants	4 Participants

SECONDARY outcome

Timeframe: 28-35 days

Pulmonary embolism confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy, and as adjudicated by the VTE events committee

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=1001 Participants qd (once daily) oral	Enoxaparin n=992 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Pulmonary Embolism During Treatment Period	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 28-35 days

All cause death, as adjudicated by the VTE events committee

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=1001 Participants qd (once daily) oral	Enoxaparin n=992 Participants 40mg qd (once daily) subcutaneous
Number of Participants Who Died During Treatment Period	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Patients with any data available during follow-up

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=942 Participants qd (once daily) oral	Enoxaparin n=951 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period asymptomatic Deep Vein Thrombosis	0 Participants	1 Participants
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period Pulmonary Embolism	1 Participants	2 Participants
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period death	0 Participants	1 Participants
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period Total VTE and all-cause mortality	2 Participants	4 Participants
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period symptomatic Deep Vein Thrombosis	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 28-35 days

Population: All patients who had been randomised, had taken at least 1 dose of oral or subcutaneous trial medication.

Major bleeding events were defined as * fatal * clinically overt associated with loss of haemoglobin \>=20g/L in excess of what was expected * clinically overt leading to the transfusion of \>=2 units packed cells or whole blood in excess of what was expected * symptomatic retroperitoneal, intracranial, intraocular or intraspinal * requiring treatment cessation * leading to re-operation Clinically-relevant was 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 * any other bleeding event considered clinically relevant by the investigator Any bleeding events were defined as major, clinically-relevant and minor bleeding events. Minor bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=1010 Participants qd (once daily) oral	Enoxaparin n=1003 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period Major bleeding events	14 Participants	9 Participants
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period Major and clinically relevant bleeding events	37 Participants	29 Participants
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period Any bleeding events	98 Participants	83 Participants

SECONDARY outcome

Timeframe: Day 1

Population: Treated and operated patients

Number of treated and operated patients with required blood transfusion on day of surgery.

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=1001 Participants qd (once daily) oral	Enoxaparin n=992 Participants 40mg qd (once daily) subcutaneous
Blood Transfusion Transfusions required	246 participants	237 participants
Blood Transfusion Missing	4 participants	7 participants

SECONDARY outcome

Timeframe: Day 1

Population: Treated and operated patients

Volume of blood loss for treated and operated patients during surgery.

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=967 Participants qd (once daily) oral	Enoxaparin n=957 Participants 40mg qd (once daily) subcutaneous
Volume of Blood Loss	404.9 mL Standard Deviation 259.67	411.0 mL Standard Deviation 275.38

SECONDARY outcome

Timeframe: First administration to end of study

Population: Treated patients

Frequency of patients with possible clinically significant abnormalities.

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=966 Participants qd (once daily) oral	Enoxaparin n=962 Participants 40mg qd (once daily) subcutaneous
Laboratory Analyses ALT decrease N=(966;962)	0 participants	0 participants
Laboratory Analyses Bilirubin increase N=(966;962)	3 participants	1 participants
Laboratory Analyses AST decrease N=(964;962)	0 participants	0 participants
Laboratory Analyses ALT increase N=(966;962)	34 participants	67 participants
Laboratory Analyses Bilirubin decrease N=(966;962)	0 participants	0 participants
Laboratory Analyses AST increase N=(964;962)	28 participants	44 participants

Adverse Events

Dabigatran 220mg

Serious events: 57 serious events

Other events: 389 other events

Deaths: 0 deaths

Enoxaparin

Serious events: 59 serious events

Other events: 389 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Dabigatran 220mg n=1010 participants at risk qd (once daily) oral	Enoxaparin n=1003 participants at risk 40mg qd (once daily) subcutaneous
Gastrointestinal disorders Constipation	9.9% 100/1010 • 31 - 38 days Treatment emergent events (last medication + 3 days)	10.2% 102/1003 • 31 - 38 days Treatment emergent events (last medication + 3 days)
Gastrointestinal disorders Nausea	16.0% 162/1010 • 31 - 38 days Treatment emergent events (last medication + 3 days)	16.6% 166/1003 • 31 - 38 days Treatment emergent events (last medication + 3 days)
Gastrointestinal disorders Vomiting	10.9% 110/1010 • 31 - 38 days Treatment emergent events (last medication + 3 days)	9.4% 94/1003 • 31 - 38 days Treatment emergent events (last medication + 3 days)
General disorders Pyrexia	6.1% 62/1010 • 31 - 38 days Treatment emergent events (last medication + 3 days)	8.0% 80/1003 • 31 - 38 days Treatment emergent events (last medication + 3 days)
Investigations Haemoglobin decreased	5.5% 56/1010 • 31 - 38 days Treatment emergent events (last medication + 3 days)	6.2% 62/1003 • 31 - 38 days Treatment emergent events (last medication + 3 days)
Vascular disorders Hypotension	6.0% 61/1010 • 31 - 38 days Treatment emergent events (last medication + 3 days)	5.1% 51/1003 • 31 - 38 days Treatment emergent events (last medication + 3 days)

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