Arthroplasty, Replacement, Knee, Venous Thrombosis
Conditions
Brief summary
The goal of this study is to evaluate the comparative efficacy and safety of three different doses ( 110 mg, 150 mg, 220 mg) of BIBR 1048 (Dabigatran etexilate) orally, compared to placebo, in prevention of venous thromboembolism in patient with primary elective total knee replacement surgery, and to evaluate dose-response.
Interventions
DRUGDabigatran etexilate
Dabigatran etexilate 110 mg capsule, once a day, oral administration
DRUGDabigatran Etexilate
Dabigatran etexilate 220 mg capsule, once a day, oral administration
DRUGplacebo
matching placebo capsule, once a day, oral administration
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria 1. Patients scheduled to undergo a primary, unilateral elective total knee replacement 2. Male or Female 20 years of age or order 3. Patients weighing at least 40 kg 4. Written informed consent prior to the start of study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period. | 2 weeks study medication | number of participants with the composite endpoint (total Venous Thromboembolic Event (VTE) and all cause mortality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Have a Composite of Major VTE (Defined as Proximal DVT and PE) and VTE Related Mortality | 2 weeks | Number of participants with the composite of major VTE (defined as proximal DVT and PE) and VTE related mortality |
| Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period | 2 weeks | Number of participants who have Proximal DVT during treatment period |
| Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis) | 2 weeks | Number of Participants expressing DVT with symptoms |
| Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period | 2 weeks | Number of participants who have Total DVT during treatment period |
| Number of Participants With Pulmonary Embolism During Treatment Period | 2 weeks | Pulmonary embolism confirmed by pulmonary scintigraphy, pulmonary angiography or contrast CT. |
| Number of Participants Who Died During Treatment Period | 2 weeks | All cause death, as adjudicated by the VTE events committee. |
| Number of Participants With Bleeding Events During Treatment Period | 2 weeks | 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. |
| Blood Transfusion | Day 0 | Blood transfusion for treated and operated patients on Day of surgery. |
| Volume of Blood Loss | Day 0 | Volume of blood loss for treated and operated patients during surgery. |
| Laboratory Analyses | First administration to end of study | Frequency of patients with possible clinically significant abnormalities. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group With Placebo Patients were treated with matching Placebo. | 124 |
| Dabigatran Etexilate 110 mg Patients were treated with 110mg dabigatran etexilate once daily. | 133 |
| Dabigatran Etexilate 150 mg Patients were treated with 150mg dabigatran etexilate once daily. | 126 |
| Dabigatran Etexilate 220 mg Patients were treated with 220mg dabigatran etexilate once daily. | 129 |
| Total | 512 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 9 | 9 | 10 |
| Overall Study | unsuitable medical history was found | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Treatment Group With Placebo | Dabigatran Etexilate 110 mg | Dabigatran Etexilate 150 mg | Dabigatran Etexilate 220 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 71.3 years STANDARD_DEVIATION 8.5 | 71.3 years STANDARD_DEVIATION 7.9 | 70.9 years STANDARD_DEVIATION 7.7 | 72.7 years STANDARD_DEVIATION 6.8 | 71.6 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 105 Participants | 106 Participants | 105 Participants | 109 Participants | 425 Participants |
| Sex: Female, Male Male | 19 Participants | 27 Participants | 21 Participants | 20 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 62 / 124 | 47 / 133 | 60 / 126 | 55 / 129 |
| serious Total, serious adverse events | 2 / 124 | 3 / 133 | 3 / 126 | 2 / 129 |
Outcome results
Primary
Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period.
number of participants with the composite endpoint (total Venous Thromboembolic Event (VTE) and all cause mortality
Time frame: 2 weeks study medication
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group With Placebo | 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 |
| Dabigatran Etexilate 110 mg | Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period. | 39.6 percentage of participants |
| Dabigatran Etexilate 150 mg | Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period. | 32.7 percentage of participants |
| Dabigatran Etexilate 220 mg | Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period. | 24 percentage of participants |
Comparison: Superiority of dabigatran etexilate to placebo was tested by means of hierarchical tests. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.p-value: 0.015595% CI: [-30.2, -3.4]normal approximation method
Comparison: Superiority of dabigatran etexilate to placebo was tested by means of hierarchical tests. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.p-value: 0.000695% CI: [-37, -10.5]normal approximation method
Comparison: Superiority of dabigatran etexilate to placebo was tested by means of hierarchical tests. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.p-value: <0.000195% CI: [-45.4, -19.6]normal approximation method
Secondary
Blood Transfusion
Blood transfusion for treated and operated patients on Day of surgery.
Time frame: Day 0
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group With Placebo | Blood Transfusion | Autologous | 75 participants |
| Treatment Group With Placebo | Blood Transfusion | Autologous and homologous | 0 participants |
| Treatment Group With Placebo | Blood Transfusion | Homologous | 5 participants |
| Dabigatran Etexilate 110 mg | Blood Transfusion | Autologous | 82 participants |
| Dabigatran Etexilate 110 mg | Blood Transfusion | Autologous and homologous | 0 participants |
| Dabigatran Etexilate 110 mg | Blood Transfusion | Homologous | 4 participants |
| Dabigatran Etexilate 150 mg | Blood Transfusion | Homologous | 4 participants |
| Dabigatran Etexilate 150 mg | Blood Transfusion | Autologous | 77 participants |
| Dabigatran Etexilate 150 mg | Blood Transfusion | Autologous and homologous | 0 participants |
| Dabigatran Etexilate 220 mg | Blood Transfusion | Autologous | 76 participants |
| Dabigatran Etexilate 220 mg | Blood Transfusion | Autologous and homologous | 3 participants |
| Dabigatran Etexilate 220 mg | Blood Transfusion | Homologous | 2 participants |
Secondary
Laboratory Analyses
Frequency of patients with possible clinically significant abnormalities.
Time frame: First administration to end of study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group With Placebo | Laboratory Analyses | AST increase N=(120;131;122;126) | 2 participants |
| Treatment Group With Placebo | Laboratory Analyses | AST decrease N=(120;131;122;126) | 0 participants |
| Treatment Group With Placebo | Laboratory Analyses | ALT increase N=(120;131;122;126) | 2 participants |
| Treatment Group With Placebo | Laboratory Analyses | ALT decrease N=(120;131;122;126) | 0 participants |
| Treatment Group With Placebo | Laboratory Analyses | Bilirubin increase N=(120;130;122;127) | 0 participants |
| Treatment Group With Placebo | Laboratory Analyses | Bilirubin decrease N=(120;130;122;127) | 0 participants |
| Dabigatran Etexilate 110 mg | Laboratory Analyses | Bilirubin decrease N=(120;130;122;127) | 0 participants |
| Dabigatran Etexilate 110 mg | Laboratory Analyses | ALT decrease N=(120;131;122;126) | 0 participants |
| Dabigatran Etexilate 110 mg | Laboratory Analyses | AST increase N=(120;131;122;126) | 1 participants |
| Dabigatran Etexilate 110 mg | Laboratory Analyses | ALT increase N=(120;131;122;126) | 0 participants |
| Dabigatran Etexilate 110 mg | Laboratory Analyses | AST decrease N=(120;131;122;126) | 0 participants |
| Dabigatran Etexilate 110 mg | Laboratory Analyses | Bilirubin increase N=(120;130;122;127) | 1 participants |
| Dabigatran Etexilate 150 mg | Laboratory Analyses | AST decrease N=(120;131;122;126) | 0 participants |
| Dabigatran Etexilate 150 mg | Laboratory Analyses | ALT increase N=(120;131;122;126) | 1 participants |
| Dabigatran Etexilate 150 mg | Laboratory Analyses | ALT decrease N=(120;131;122;126) | 0 participants |
| Dabigatran Etexilate 150 mg | Laboratory Analyses | Bilirubin decrease N=(120;130;122;127) | 0 participants |
| Dabigatran Etexilate 150 mg | Laboratory Analyses | Bilirubin increase N=(120;130;122;127) | 0 participants |
| Dabigatran Etexilate 150 mg | Laboratory Analyses | AST increase N=(120;131;122;126) | 0 participants |
| Dabigatran Etexilate 220 mg | Laboratory Analyses | Bilirubin increase N=(120;130;122;127) | 0 participants |
| Dabigatran Etexilate 220 mg | Laboratory Analyses | Bilirubin decrease N=(120;130;122;127) | 0 participants |
| Dabigatran Etexilate 220 mg | Laboratory Analyses | AST decrease N=(120;131;122;126) | 0 participants |
| Dabigatran Etexilate 220 mg | Laboratory Analyses | ALT decrease N=(120;131;122;126) | 0 participants |
| Dabigatran Etexilate 220 mg | Laboratory Analyses | AST increase N=(120;131;122;126) | 0 participants |
| Dabigatran Etexilate 220 mg | Laboratory Analyses | ALT increase N=(120;131;122;126) | 0 participants |
Secondary
Number of Participants Who Died During Treatment Period
All cause death, as adjudicated by the VTE events committee.
Time frame: 2 weeks
Population: FAS-op
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group With Placebo | Number of Participants Who Died During Treatment Period | 0.0 percentage of participants |
| Dabigatran Etexilate 110 mg | Number of Participants Who Died During Treatment Period | 0.0 percentage of participants |
| Dabigatran Etexilate 150 mg | Number of Participants Who Died During Treatment Period | 0.0 percentage of participants |
| Dabigatran Etexilate 220 mg | Number of Participants Who Died During Treatment Period | 0.0 percentage of participants |
Secondary
Number of Participants With Bleeding Events During Treatment Period
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.
Time frame: 2 weeks
Population: Safety set - Safety set includes all patients who were randomly assigned to the treatment, received at least one oral dose and went through surgery.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group With Placebo | Number of Participants With Bleeding Events During Treatment Period | Major bleeding events | 1 participants |
| Treatment Group With Placebo | Number of Participants With Bleeding Events During Treatment Period | Any bleeding events | 10 participants |
| Treatment Group With Placebo | Number of Participants With Bleeding Events During Treatment Period | Major and clinically relevant bleeding events | 4 participants |
| Dabigatran Etexilate 110 mg | Number of Participants With Bleeding Events During Treatment Period | Major bleeding events | 1 participants |
| Dabigatran Etexilate 110 mg | Number of Participants With Bleeding Events During Treatment Period | Any bleeding events | 13 participants |
| Dabigatran Etexilate 110 mg | Number of Participants With Bleeding Events During Treatment Period | Major and clinically relevant bleeding events | 1 participants |
| Dabigatran Etexilate 150 mg | Number of Participants With Bleeding Events During Treatment Period | Major and clinically relevant bleeding events | 1 participants |
| Dabigatran Etexilate 150 mg | Number of Participants With Bleeding Events During Treatment Period | Major bleeding events | 0 participants |
| Dabigatran Etexilate 150 mg | Number of Participants With Bleeding Events During Treatment Period | Any bleeding events | 13 participants |
| Dabigatran Etexilate 220 mg | Number of Participants With Bleeding Events During Treatment Period | Major bleeding events | 3 participants |
| Dabigatran Etexilate 220 mg | Number of Participants With Bleeding Events During Treatment Period | Any bleeding events | 14 participants |
| Dabigatran Etexilate 220 mg | Number of Participants With Bleeding Events During Treatment Period | Major and clinically relevant bleeding events | 5 participants |
Comparison: Comparison versus Placebo for the category major bleeding eventsp-value: 1Fisher Exact
Comparison: Comparison versus Placebo for the category major bleeding eventsp-value: 0.496Fisher Exact
Comparison: Comparison versus Placebo for the category major bleeding eventsp-value: 0.6223Fisher Exact
Comparison: Absolute difference versus Placebo for the category major and clinically relevant bleeding eventsp-value: 0.151395% CI: [-5.9, 1]normal approximation method
Comparison: Absolute difference versus Placebo for the category major and clinically relevant bleeding eventsp-value: 0.169695% CI: [-5.9, 1]normal approximation method
Comparison: Absolute difference versus Placebo for the category major and clinically relevant bleeding eventsp-value: 0.780295% CI: [-3.9, 5.2]normal approximation method
Comparison: Absolute difference versus Placebo for the category any bleeding eventsp-value: 0.631395% CI: [-5.3, 8.7]normal approximation method
Comparison: Absolute difference versus Placebo for the category any bleeding eventsp-value: 0.537795% CI: [-4.9, 9.4]normal approximation method
Comparison: Absolute difference versus Placebo for the category any bleeding eventsp-value: 0.449395% CI: [-4.4, 10]normal approximation method
Secondary
Number of Participants With Pulmonary Embolism During Treatment Period
Pulmonary embolism confirmed by pulmonary scintigraphy, pulmonary angiography or contrast CT.
Time frame: 2 weeks
Population: FAS-op
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group With Placebo | Number of Participants With Pulmonary Embolism During Treatment Period | 0.0 percentage of participants |
| Dabigatran Etexilate 110 mg | Number of Participants With Pulmonary Embolism During Treatment Period | 0.0 percentage of participants |
| Dabigatran Etexilate 150 mg | Number of Participants With Pulmonary Embolism During Treatment Period | 0.0 percentage of participants |
| Dabigatran Etexilate 220 mg | Number of Participants With Pulmonary Embolism During Treatment Period | 0.0 percentage of participants |
Secondary
Percentage of Participants Who Have a Composite of Major VTE (Defined as Proximal DVT and PE) and VTE Related Mortality
Number of participants with the composite of major VTE (defined as proximal DVT and PE) and VTE related mortality
Time frame: 2 weeks
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group With Placebo | 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 |
| Dabigatran Etexilate 110 mg | Percentage of Participants Who Have a Composite of Major VTE (Defined as Proximal DVT and PE) and VTE Related Mortality | 1.7 percentage of participants |
| Dabigatran Etexilate 150 mg | Percentage of Participants Who Have a Composite of Major VTE (Defined as Proximal DVT and PE) and VTE Related Mortality | 1.8 percentage of participants |
| Dabigatran Etexilate 220 mg | Percentage of Participants Who Have a Composite of Major VTE (Defined as Proximal DVT and PE) and VTE Related Mortality | 0 percentage of participants |
Comparison: Superiority of dabigatran etexilate to placebo was tested. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.p-value: 0.112495% CI: [-9.1, 1]normal approximation method
Comparison: Superiority of dabigatran etexilate to placebo was tested. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.p-value: 0.118395% CI: [-9.1, 1.1]normal approximation method
Comparison: Superiority of dabigatran etexilate to placebo was tested. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.p-value: 0.013895% CI: [-10.3, -1.3]normal approximation method
Secondary
Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period
Number of participants who have Proximal DVT during treatment period
Time frame: 2 weeks
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group With Placebo | Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period | 5.8 percentage of participants |
| Dabigatran Etexilate 110 mg | Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period | 1.7 percentage of participants |
| Dabigatran Etexilate 150 mg | Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period | 1.8 percentage of participants |
| Dabigatran Etexilate 220 mg | Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period | 0 percentage of participants |
Comparison: Superiority of dabigatran etexilate to placebo was tested. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.~The dabigatran groups were compared to the placebo group.. The null hypotheses are Ho: placebo = 220mg, Ho: placebo = 150mg and Ho: placebo = 110mg. ,All comparisons were two-sided with a significance level of 5%. Confidence intervals were two-sided with a level of 95%.p-value: 0.112495% CI: [-9.1, 1]normal approximation method
Comparison: Superiority of dabigatran etexilate to placebo was tested. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.~The dabigatran groups were compared to the placebo group.. The null hypotheses are Ho: placebo = 220mg, Ho: placebo = 150mg and Ho: placebo = 110mg. ,All comparisons were two-sided with a significance level of 5%. Confidence intervals were two-sided with a level of 95%.p-value: 0.118395% CI: [-9.1, 1.1]normal approximation method
Comparison: Superiority of dabigatran etexilate to placebo was tested. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.~The dabigatran groups were compared to the placebo group.. The null hypotheses are Ho: placebo = 220mg, Ho: placebo = 150mg and Ho: placebo = 110mg. ,All comparisons were two-sided with a significance level of 5%. Confidence intervals were two-sided with a level of 95%.p-value: 0.013895% CI: [-10.3, -1.3]normal approximation method
Secondary
Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period
Number of participants who have Total DVT during treatment period
Time frame: 2 weeks
Population: FAS-tDVT - FAS-tDVT includes all patients who were randomised, treated, operated, and had evaluable venogram or confirmed symptomatic DVT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group With Placebo | Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period | 56.4 percentage of participants |
| Dabigatran Etexilate 110 mg | Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period | 39.6 percentage of participants |
| Dabigatran Etexilate 150 mg | Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period | 32.7 percentage of participants |
| Dabigatran Etexilate 220 mg | Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period | 24.0 percentage of participants |
Comparison: Superiority of dabigatran etexilate to placebo was tested. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.~The dabigatran groups were compared to the placebo group.. The null hypotheses are Ho: placebo = 220mg, Ho: placebo = 150mg and Ho: placebo = 110mg. ,All comparisons were two-sided with a significance level of 5%. Confidence intervals were two-sided with a level of 95%.p-value: 0.015595% CI: [-30.2, -3.4]normal approximation method
Comparison: Superiority of dabigatran etexilate to placebo was tested. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.~The dabigatran groups were compared to the placebo group.. The null hypotheses are Ho: placebo = 220mg, Ho: placebo = 150mg and Ho: placebo = 110mg. ,All comparisons were two-sided with a significance level of 5%. Confidence intervals were two-sided with a level of 95%.p-value: 0.000695% CI: [-37, -10.5]normal approximation method
Comparison: Superiority of dabigatran etexilate to placebo was tested. Statistical inference was made on the basis of the normal approximation of two independent binomial distributions.~The dabigatran groups were compared to the placebo group.. The null hypotheses are Ho: placebo = 220mg, Ho: placebo = 150mg and Ho: placebo = 110mg. ,All comparisons were two-sided with a significance level of 5%. Confidence intervals were two-sided with a level of 95%.p-value: <0.000195% CI: [-45.4, -19.6]normal approximation method
Secondary
Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis)
Number of Participants expressing DVT with symptoms
Time frame: 2 weeks
Population: FAS-op - FAS-op includes all patients who were randomly assigned to the treatment, received at least one oral dose and went through surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group With Placebo | Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis) | 1.6 Percentage of participants |
| Dabigatran Etexilate 110 mg | Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis) | 0.8 Percentage of participants |
| Dabigatran Etexilate 150 mg | Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis) | 1.6 Percentage of participants |
| Dabigatran Etexilate 220 mg | Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis) | 0.8 Percentage of participants |
Comparison: Superiority of dabigatran etexilate to placebo was tested based on Fisher's exact test.~The dabigatran groups were compared to the placebo group.. The null hypotheses are Ho: placebo = 220mg, Ho: placebo = 150mg and Ho: placebo = 110mg. ,All comparisons were two-sided with a significance level of 5%. Confidence intervals were two-sided with a level of 95%.p-value: 0.6107Fisher Exact
Comparison: Superiority of dabigatran etexilate to placebo was tested based on Fisher's exact test.~The dabigatran groups were compared to the placebo group.. The null hypotheses are Ho: placebo = 220mg, Ho: placebo = 150mg and Ho: placebo = 110mg. ,All comparisons were two-sided with a significance level of 5%. Confidence intervals were two-sided with a level of 95%.p-value: 1Fisher Exact
Comparison: Superiority of dabigatran etexilate to placebo was tested based on Fisher's exact test.~The dabigatran groups were compared to the placebo group.. The null hypotheses are Ho: placebo = 220mg, Ho: placebo = 150mg and Ho: placebo = 110mg. ,All comparisons were two-sided with a significance level of 5%. Confidence intervals were two-sided with a level of 95%.p-value: 0.6162Fisher Exact
Secondary
Volume of Blood Loss
Volume of blood loss for treated and operated patients during surgery.
Time frame: Day 0
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group With Placebo | Volume of Blood Loss | 82.8 mL | Standard Deviation 132 |
| Dabigatran Etexilate 110 mg | Volume of Blood Loss | 90.5 mL | Standard Deviation 128 |
| Dabigatran Etexilate 150 mg | Volume of Blood Loss | 67.5 mL | Standard Deviation 96 |
| Dabigatran Etexilate 220 mg | Volume of Blood Loss | 77.3 mL | Standard Deviation 130.6 |