Trial Outcomes & Findings for RE-MODEL Dabigatran Etexilate 150mg or 220mg Once Daily (o.d.) Versus (v.s.) Enoxaparin 40mg o.d. for Prevention of Thrombosis After Knee Surgery (NCT NCT00168805)

Last Updated: 2014-05-19

Results Overview

Total Venous Thromboembolic Event (VTE) includes both proximal and distal deep vein thrombosis (DVT) (detected by routine bilateral venography), symptomatic DVT (confirmed by venous compression 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

2101 participants

Primary outcome timeframe

First administration until 6-10 days

Results posted on

2014-05-19

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 8 days. The study period is from first administration of study medication until day 84 - 91.

Whilst 2101 patients were enrolled/randomised to treatment prior to surgery in this trial, only 2076 started treatment. Therefore, 25 patients were randomised but not treated (treatment was planned to start post surgery).

Participant milestones

Participant milestones
Measure	Dabigatran 220mg qd (once daily) oral	Dabigatran 150mg qd (once daily) oral	Enoxaparin 40mg qd (once daily) subcutaneous
Overall Study STARTED	679	703	694
Overall Study COMPLETED	608	625	616
Overall Study NOT COMPLETED	71	78	78
Treatment STARTED	679	703	694
Treatment COMPLETED	630	647	632
Treatment NOT COMPLETED	49	56	62

Reasons for withdrawal

Reasons for withdrawal
Measure	Dabigatran 220mg qd (once daily) oral	Dabigatran 150mg qd (once daily) oral	Enoxaparin 40mg qd (once daily) subcutaneous
Overall Study Adverse Event	7	11	16
Overall Study Protocol Violation	12	11	8
Overall Study Lost to Follow-up	12	17	11
Overall Study Withdrawal by Subject	16	18	21
Overall Study Other	24	21	22
Treatment Adverse Event	25	26	32
Treatment Protocol Violation	3	5	5
Treatment Withdrawal by Subject	3	7	8
Treatment Other	18	18	17

Baseline Characteristics

RE-MODEL Dabigatran Etexilate 150mg or 220mg Once Daily (o.d.) Versus (v.s.) Enoxaparin 40mg o.d. for Prevention of Thrombosis After Knee Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dabigatran 220mg n=679 Participants qd (once daily) oral	Dabigatran 150mg n=703 Participants qd (once daily) oral	Enoxaparin n=694 Participants 40mg qd (once daily) subcutaneous	Total n=2076 Participants Total of all reporting groups
Age, Continuous	67.3 Years STANDARD_DEVIATION 9.0 • n=5 Participants	67.5 Years STANDARD_DEVIATION 8.8 • n=7 Participants	68.3 Years STANDARD_DEVIATION 8.8 • n=5 Participants	67.7 Years STANDARD_DEVIATION 8.9 • n=4 Participants
Sex: Female, Male Female	441 Participants n=5 Participants	451 Participants n=7 Participants	478 Participants n=5 Participants	1370 Participants n=4 Participants
Sex: Female, Male Male	238 Participants n=5 Participants	252 Participants n=7 Participants	216 Participants n=5 Participants	706 Participants n=4 Participants
Body Mass Index N=(677;702;692;2071)	29.9 kg/m^2 STANDARD_DEVIATION 4.9 • n=5 Participants	30.1 kg/m^2 STANDARD_DEVIATION 5.0 • n=7 Participants	29.8 kg/m^2 STANDARD_DEVIATION 4.9 • n=5 Participants	29.9 kg/m^2 STANDARD_DEVIATION 4.9 • n=4 Participants

PRIMARY outcome

Timeframe: First administration until 6-10 days

Population: Full Analysis Set (all patients who had surgery and were randomised, received treatment, had an evaluable venogram for distal and proximal Deep Vein Thrombosis, or had confirmed symptomatic Deep Vein Thrombosis, Pulmonary Embolism, or had died)

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=503 Participants qd (once daily) oral	Dabigatran 150mg n=526 Participants qd (once daily) oral	Enoxaparin n=512 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period	183 Participants	213 Participants	193 Participants

SECONDARY outcome

Timeframe: First administration until 6-10 days

Population: Full Analysis Set - major (all patients who had surgery and were randomised, received treatment, had an evaluable venogram for proximal Deep Vein Thrombosis, or had confirmed symptomatic Deep Vein Thrombosis, Pulmonary Embolism, or had died by a Venous Thromboembolic Event-related death)

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=506 Participants qd (once daily) oral	Dabigatran 150mg n=527 Participants qd (once daily) oral	Enoxaparin n=511 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period	13 Participants	20 Participants	18 Participants

SECONDARY outcome

Timeframe: First administration until 6-10 days

Population: Full Analysis Set - pDVT (all patients who had surgery and were randomised, received treatment, had an evaluable venogram for proximal Deep Vein Thrombosis, or had confirmed symptomatic Deep Vein Thrombosis)

Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=506 Participants qd (once daily) oral	Dabigatran 150mg n=525 Participants qd (once daily) oral	Enoxaparin n=510 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Proximal Deep Vein Thrombosis During Treatment Period	13 Participants	18 Participants	17 Participants

SECONDARY outcome

Timeframe: First administration until 6-10 days

Population: Full Analysis Set - tDVT (all patients who had surgery and were randomised, received treatment, had an evaluable venogram, or had confirmed symptomatic Deep Vein Thrombosis)

Total Deep Vein Thrombosis as adjudicated by the VTE events committee

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=503 Participants qd (once daily) oral	Dabigatran 150mg n=524 Participants qd (once daily) oral	Enoxaparin n=511 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Total Deep Vein Thrombosis During Treatment Period	182 Participants	211 Participants	192 Participants

SECONDARY outcome

Timeframe: First administration until 6-10 days

Population: Full Analysis Set - op (all patients who are treated and operated)

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

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=675 Participants qd (once daily) oral	Dabigatran 150mg n=696 Participants qd (once daily) oral	Enoxaparin n=685 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period	1 Participants	3 Participants	8 Participants

SECONDARY outcome

Timeframe: First administration until 6-10 days

Population: Full Analysis Set - op

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=675 Participants qd (once daily) oral	Dabigatran 150mg n=696 Participants qd (once daily) oral	Enoxaparin n=685 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Pulmonary Embolism During Treatment Period	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: First administration until 6-10 days

Population: Full Analysis Set - op

All cause death, as adjudicated by the VTE events committee

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=675 Participants qd (once daily) oral	Dabigatran 150mg n=696 Participants qd (once daily) oral	Enoxaparin n=685 Participants 40mg qd (once daily) subcutaneous
Number of Participants Who Died During Treatment Period	1 Participants	1 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=658 Participants qd (once daily) oral	Dabigatran 150mg n=679 Participants qd (once daily) oral	Enoxaparin n=665 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period Total VTE and all-cause mortality	4 Participants	3 Participants	2 Participants
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period asymptotic Deep Vein Thrombosis	0 Participants	1 Participants	0 Participants
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period symptotic Deep Vein Thrombosis	1 Participants	2 Participants	0 Participants
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period Pulmonary Embolism	2 Participants	0 Participants	0 Participants
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period death	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: First administration until 6-10 days

Population: Treated set

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 greater than or equal to 25 cm² * wound hematoma greater than or equal to 100 cm² * spontaneous nose bleed lasting longer than 5 min * macroscopic hematuria spontaneous or lasting longer than 24 hours if associated with an intervention * spontaneous rectal bleeding (more than a spot on toilet paper) * gingival bleeding lasting longer than 5 min * any other bleeding event considered clinically relevant by the investigator 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=679 Participants qd (once daily) oral	Dabigatran 150mg n=703 Participants qd (once daily) oral	Enoxaparin n=694 Participants 40mg qd (once daily) subcutaneous
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period Major	10 Participants	9 Participants	9 Participants
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period Clinically relevant	40 Participants	48 Participants	37 Participants
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period Minor	60 Participants	59 Participants	69 Participants
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period None	569 Participants	587 Participants	579 Participants

SECONDARY outcome

Timeframe: Day 1

Blood transfusion for treated and operated patients on Day of surgery.

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=675 Participants qd (once daily) oral	Dabigatran 150mg n=696 Participants qd (once daily) oral	Enoxaparin n=685 Participants 40mg qd (once daily) subcutaneous
Blood Transfusion Patients with >=1 transfusions	242 participants	253 participants	265 participants
Blood Transfusion Patients with >=1 non-autologous transfusions	87 participants	86 participants	120 participants

SECONDARY outcome

Timeframe: Day 1

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

Outcome measures

Outcome measures
Measure	Dabigatran 220mg n=650 Participants qd (once daily) oral	Dabigatran 150mg n=669 Participants qd (once daily) oral	Enoxaparin n=658 Participants 40mg qd (once daily) subcutaneous
Volume of Blood Loss	187 mL Standard Deviation 258	190 mL Standard Deviation 250	191 mL Standard Deviation 254

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=621 Participants qd (once daily) oral	Dabigatran 150mg n=645 Participants qd (once daily) oral	Enoxaparin n=637 Participants 40mg qd (once daily) subcutaneous
Laboratory Analyses AST increase N=(620;645;636)	9 participants	6 participants	9 participants
Laboratory Analyses AST decrease N=(620;645;636)	0 participants	0 participants	0 participants
Laboratory Analyses ALT increase N=(621;645;637)	16 participants	21 participants	24 participants
Laboratory Analyses ALT decrease N=(621;645;637)	0 participants	0 participants	0 participants
Laboratory Analyses Bilirubin increase N=(619;644;635)	19 participants	23 participants	14 participants
Laboratory Analyses Bilirubin decrease N=(619;644;635)	0 participants	0 participants	0 participants

Adverse Events

Dabigatran 220mg

Serious events: 31 serious events

Other events: 405 other events

Deaths: 0 deaths

Dabigatran 150mg

Serious events: 44 serious events

Other events: 438 other events

Deaths: 0 deaths

Enoxaparin

Serious events: 43 serious events

Other events: 426 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Dabigatran 220mg n=679 participants at risk qd (once daily) oral	Dabigatran 150mg n=703 participants at risk qd (once daily) oral	Enoxaparin n=694 participants at risk 40mg qd (once daily) subcutaneous
Gastrointestinal disorders Constipation	10.5% 71/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	9.2% 65/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	11.1% 77/694 • First administration to end of study Treatment emergent events (last medication + 3 days)
Gastrointestinal disorders Diarrhoea	4.0% 27/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	5.8% 41/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	3.5% 24/694 • First administration to end of study Treatment emergent events (last medication + 3 days)
Gastrointestinal disorders Nausea	20.0% 136/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	19.6% 138/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	24.9% 173/694 • First administration to end of study Treatment emergent events (last medication + 3 days)
Gastrointestinal disorders Vomiting	16.5% 112/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	16.1% 113/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	17.0% 118/694 • First administration to end of study Treatment emergent events (last medication + 3 days)
General disorders Oedema peripheral	7.4% 50/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	7.8% 55/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	7.5% 52/694 • First administration to end of study Treatment emergent events (last medication + 3 days)
General disorders Pyrexia	8.0% 54/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	9.1% 64/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	8.9% 62/694 • First administration to end of study Treatment emergent events (last medication + 3 days)
Injury, poisoning and procedural complications Post procedural haematoma	4.1% 28/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	4.4% 31/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	5.2% 36/694 • First administration to end of study Treatment emergent events (last medication + 3 days)
Psychiatric disorders Insomnia	9.7% 66/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	9.2% 65/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	9.9% 69/694 • First administration to end of study Treatment emergent events (last medication + 3 days)
Vascular disorders Deep vein thrombosis	11.5% 78/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	15.1% 106/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	12.8% 89/694 • First administration to end of study Treatment emergent events (last medication + 3 days)
Vascular disorders Hypotension	2.8% 19/679 • First administration to end of study Treatment emergent events (last medication + 3 days)	5.3% 37/703 • First administration to end of study Treatment emergent events (last medication + 3 days)	4.9% 34/694 • First administration to end of study 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