Trial Outcomes & Findings for A Study of BIBR 1048 in Prevention of Venous Thromboembolism in Patients With TKR Surgery. (NCT NCT00246025)
NCT ID: NCT00246025
Last Updated: 2014-06-09
Results Overview
number of participants with the composite endpoint (total Venous Thromboembolic Event (VTE) and all cause mortality
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
512 participants
Primary outcome timeframe
2 weeks study medication
Results posted on
2014-06-09
Participant Flow
Participant milestones
| Measure |
Treatment Group With Placebo
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
124
|
133
|
126
|
129
|
|
Overall Study
COMPLETED
|
114
|
124
|
116
|
116
|
|
Overall Study
NOT COMPLETED
|
10
|
9
|
10
|
13
|
Reasons for withdrawal
| Measure |
Treatment Group With Placebo
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
7
|
9
|
9
|
10
|
|
Overall Study
Withdrawal by Subject
|
3
|
0
|
1
|
2
|
|
Overall Study
unsuitable medical history was found
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Study of BIBR 1048 in Prevention of Venous Thromboembolism in Patients With TKR Surgery.
Baseline characteristics by cohort
| Measure |
Treatment Group With Placebo
n=124 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=133 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=126 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=129 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
Total
n=512 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
71.3 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
71.3 years
STANDARD_DEVIATION 7.9 • n=7 Participants
|
70.9 years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
72.7 years
STANDARD_DEVIATION 6.8 • n=4 Participants
|
71.6 years
STANDARD_DEVIATION 7.8 • n=21 Participants
|
|
Sex: Female, Male
Female
|
105 Participants
n=5 Participants
|
106 Participants
n=7 Participants
|
105 Participants
n=5 Participants
|
109 Participants
n=4 Participants
|
425 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
87 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 2 weeks study medicationPopulation: Full analysis set (FAS) - Full analysis set includes all patients who were randomly assigned to the treatment, received at least one oral dose, went through surgery, had an evaluable venogram for distal and proximal DVT, or had confirmed symptomatic DVT or PE, or died.
number of participants with the composite endpoint (total Venous Thromboembolic Event (VTE) and all cause mortality
Outcome measures
| Measure |
Treatment Group With Placebo
n=101 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=106 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=104 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=96 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period.
|
56.4 percentage of participants
|
39.6 percentage of participants
|
32.7 percentage of participants
|
24 percentage of participants
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: FAS-major - FAS-major includes all patients who were randomised, treated, operated, and had an evaluable venogram for proximal DVT or confirmed symptomatic proximal DVT, PE, or VTE-related death.
Number of participants with the composite of major VTE (defined as proximal DVT and PE) and VTE related mortality
Outcome measures
| Measure |
Treatment Group With Placebo
n=104 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=115 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=113 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=102 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Percentage of Participants Who Have a Composite of Major VTE (Defined as Proximal DVT and PE) and VTE Related Mortality
|
5.8 percentage of participants
|
1.7 percentage of participants
|
1.8 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: FAS-pDVT - FAS-pDVT includes all patients who were randomised, treated, operated, and had an evaluable venogram for proximal DVT or confirmed symptomatic proximal DVT.
Number of participants who have Proximal DVT during treatment period
Outcome measures
| Measure |
Treatment Group With Placebo
n=104 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=115 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=113 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=102 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period
|
5.8 percentage of participants
|
1.7 percentage of participants
|
1.8 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: FAS-op - FAS-op includes all patients who were randomly assigned to the treatment, received at least one oral dose and went through surgery.
Number of Participants expressing DVT with symptoms
Outcome measures
| Measure |
Treatment Group With Placebo
n=124 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=133 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=126 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=129 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis)
|
1.6 Percentage of participants
|
0.8 Percentage of participants
|
1.6 Percentage of participants
|
0.8 Percentage of participants
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: FAS-tDVT - FAS-tDVT includes all patients who were randomised, treated, operated, and had evaluable venogram or confirmed symptomatic DVT.
Number of participants who have Total DVT during treatment period
Outcome measures
| Measure |
Treatment Group With Placebo
n=101 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=106 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=104 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=96 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period
|
56.4 percentage of participants
|
39.6 percentage of participants
|
32.7 percentage of participants
|
24.0 percentage of participants
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: FAS-op
Pulmonary embolism confirmed by pulmonary scintigraphy, pulmonary angiography or contrast CT.
Outcome measures
| Measure |
Treatment Group With Placebo
n=124 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=133 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=126 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=129 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Number of Participants With Pulmonary Embolism During Treatment Period
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: FAS-op
All cause death, as adjudicated by the VTE events committee.
Outcome measures
| Measure |
Treatment Group With Placebo
n=124 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=133 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=126 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=129 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Number of Participants Who Died During Treatment Period
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: Safety set - Safety set includes all patients who were randomly assigned to the treatment, received at least one oral dose and went through surgery.
Major bleeding events were defined as * fatal * clinically overt associated with loss of haemoglobin \>=2g/dL 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 (more than a spot on toilet paper) * 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
| Measure |
Treatment Group With Placebo
n=124 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=133 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=126 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=129 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Number of Participants With Bleeding Events During Treatment Period
Major bleeding events
|
1 participants
|
1 participants
|
0 participants
|
3 participants
|
|
Number of Participants With Bleeding Events During Treatment Period
Major and clinically relevant bleeding events
|
4 participants
|
1 participants
|
1 participants
|
5 participants
|
|
Number of Participants With Bleeding Events During Treatment Period
Any bleeding events
|
10 participants
|
13 participants
|
13 participants
|
14 participants
|
SECONDARY outcome
Timeframe: Day 0Population: Safety set
Blood transfusion for treated and operated patients on Day of surgery.
Outcome measures
| Measure |
Treatment Group With Placebo
n=124 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=133 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=126 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=129 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Blood Transfusion
Autologous and homologous
|
0 participants
|
0 participants
|
0 participants
|
3 participants
|
|
Blood Transfusion
Autologous
|
75 participants
|
82 participants
|
77 participants
|
76 participants
|
|
Blood Transfusion
Homologous
|
5 participants
|
4 participants
|
4 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Day 0Population: Safety set
Volume of blood loss for treated and operated patients during surgery.
Outcome measures
| Measure |
Treatment Group With Placebo
n=124 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=133 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=126 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=129 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Volume of Blood Loss
|
82.8 mL
Standard Deviation 132.0
|
90.5 mL
Standard Deviation 128.0
|
67.5 mL
Standard Deviation 96.0
|
77.3 mL
Standard Deviation 130.6
|
SECONDARY outcome
Timeframe: First administration to end of studyFrequency of patients with possible clinically significant abnormalities.
Outcome measures
| Measure |
Treatment Group With Placebo
n=120 Participants
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=131 Participants
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=122 Participants
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=127 Participants
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Laboratory Analyses
AST increase N=(120;131;122;126)
|
2 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Laboratory Analyses
AST decrease N=(120;131;122;126)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Laboratory Analyses
ALT increase N=(120;131;122;126)
|
2 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Laboratory Analyses
ALT decrease N=(120;131;122;126)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Laboratory Analyses
Bilirubin increase N=(120;130;122;127)
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Laboratory Analyses
Bilirubin decrease N=(120;130;122;127)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Treatment Group With Placebo
Serious events: 2 serious events
Other events: 62 other events
Deaths: 0 deaths
Dabigatran Etexilate 110 mg
Serious events: 3 serious events
Other events: 47 other events
Deaths: 0 deaths
Dabigatran Etexilate 150 mg
Serious events: 3 serious events
Other events: 60 other events
Deaths: 0 deaths
Dabigatran Etexilate 220 mg
Serious events: 2 serious events
Other events: 55 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment Group With Placebo
n=124 participants at risk
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=133 participants at risk
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=126 participants at risk
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=129 participants at risk
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Infections and infestations
Post procedural infestation
|
0.00%
0/124 • First administration to end of study
|
0.75%
1/133 • First administration to end of study
|
0.00%
0/126 • First administration to end of study
|
0.00%
0/129 • First administration to end of study
|
|
Infections and infestations
Wound infection bacterial
|
0.00%
0/124 • First administration to end of study
|
0.00%
0/133 • First administration to end of study
|
0.79%
1/126 • First administration to end of study
|
0.00%
0/129 • First administration to end of study
|
|
Nervous system disorders
Diplegia
|
0.00%
0/124 • First administration to end of study
|
0.00%
0/133 • First administration to end of study
|
0.79%
1/126 • First administration to end of study
|
0.00%
0/129 • First administration to end of study
|
|
Vascular disorders
Deep vein thrombosis
|
0.81%
1/124 • First administration to end of study
|
0.00%
0/133 • First administration to end of study
|
0.00%
0/126 • First administration to end of study
|
0.00%
0/129 • First administration to end of study
|
|
Vascular disorders
Wound haemorrhage
|
0.00%
0/124 • First administration to end of study
|
0.00%
0/133 • First administration to end of study
|
0.00%
0/126 • First administration to end of study
|
0.78%
1/129 • First administration to end of study
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/124 • First administration to end of study
|
0.00%
0/133 • First administration to end of study
|
0.00%
0/126 • First administration to end of study
|
0.78%
1/129 • First administration to end of study
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/124 • First administration to end of study
|
0.75%
1/133 • First administration to end of study
|
0.00%
0/126 • First administration to end of study
|
0.00%
0/129 • First administration to end of study
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/124 • First administration to end of study
|
0.00%
0/133 • First administration to end of study
|
0.79%
1/126 • First administration to end of study
|
0.00%
0/129 • First administration to end of study
|
|
Musculoskeletal and connective tissue disorders
Muscle contracture
|
0.00%
0/124 • First administration to end of study
|
0.75%
1/133 • First administration to end of study
|
0.00%
0/126 • First administration to end of study
|
0.00%
0/129 • First administration to end of study
|
|
Investigations
Liver function test abnormal
|
0.81%
1/124 • First administration to end of study
|
0.00%
0/133 • First administration to end of study
|
0.79%
1/126 • First administration to end of study
|
0.00%
0/129 • First administration to end of study
|
|
Injury, poisoning and procedural complications
Wound secretion
|
0.00%
0/124 • First administration to end of study
|
0.00%
0/133 • First administration to end of study
|
0.79%
1/126 • First administration to end of study
|
0.00%
0/129 • First administration to end of study
|
Other adverse events
| Measure |
Treatment Group With Placebo
n=124 participants at risk
Patients were treated with matching Placebo.
|
Dabigatran Etexilate 110 mg
n=133 participants at risk
Patients were treated with 110mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 150 mg
n=126 participants at risk
Patients were treated with 150mg dabigatran etexilate once daily.
|
Dabigatran Etexilate 220 mg
n=129 participants at risk
Patients were treated with 220mg dabigatran etexilate once daily.
|
|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
1.6%
2/124 • First administration to end of study
|
4.5%
6/133 • First administration to end of study
|
6.3%
8/126 • First administration to end of study
|
3.1%
4/129 • First administration to end of study
|
|
Psychiatric disorders
Insomnia
|
11.3%
14/124 • First administration to end of study
|
5.3%
7/133 • First administration to end of study
|
11.9%
15/126 • First administration to end of study
|
9.3%
12/129 • First administration to end of study
|
|
Nervous system disorders
Headache
|
5.6%
7/124 • First administration to end of study
|
0.75%
1/133 • First administration to end of study
|
0.79%
1/126 • First administration to end of study
|
3.9%
5/129 • First administration to end of study
|
|
Vascular disorders
Deep vein thrombosis
|
23.4%
29/124 • First administration to end of study
|
17.3%
23/133 • First administration to end of study
|
7.9%
10/126 • First administration to end of study
|
10.9%
14/129 • First administration to end of study
|
|
Gastrointestinal disorders
Constipation
|
5.6%
7/124 • First administration to end of study
|
6.0%
8/133 • First administration to end of study
|
5.6%
7/126 • First administration to end of study
|
10.1%
13/129 • First administration to end of study
|
|
Gastrointestinal disorders
Diarrhoea
|
9.7%
12/124 • First administration to end of study
|
2.3%
3/133 • First administration to end of study
|
3.2%
4/126 • First administration to end of study
|
3.1%
4/129 • First administration to end of study
|
|
Gastrointestinal disorders
Stomach discomfort
|
4.0%
5/124 • First administration to end of study
|
3.0%
4/133 • First administration to end of study
|
6.3%
8/126 • First administration to end of study
|
2.3%
3/129 • First administration to end of study
|
|
Skin and subcutaneous tissue disorders
Blister
|
5.6%
7/124 • First administration to end of study
|
3.8%
5/133 • First administration to end of study
|
7.9%
10/126 • First administration to end of study
|
6.2%
8/129 • First administration to end of study
|
|
General disorders
Oedema peripheral
|
2.4%
3/124 • First administration to end of study
|
0.75%
1/133 • First administration to end of study
|
7.1%
9/126 • First administration to end of study
|
3.1%
4/129 • First administration to end of study
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.2%
4/124 • First administration to end of study
|
2.3%
3/133 • First administration to end of study
|
2.4%
3/126 • First administration to end of study
|
5.4%
7/129 • First administration to end of study
|
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