Arthroplasty, Replacement, Thromboembolism
Conditions
Brief summary
An observational cohort study on safety and efficacy of the 220 mg dose Pradaxa to generate additional data in predefined sub populations of patients at increased risk of bleeding or VTE
Interventions
None listed
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients of 18 years of age or above undergoing elective total hip or knee replacement surgery who consent in writing to their participation in this observational study
Exclusion criteria
All patients who should not be treated with Pradaxa 220 mg according to the European Summary of Product Characteristics (SPC): age of \> 75 years, renal impairment (creatinine clearance \<50 ml/min), patients with concomitant therapy of amiodarone, elevated liver enzymes \> 2 upper limit of normal (ULN) and/or hepatic impairment or liver disease expected to have any impact on survival, anaesthesia with post operative indwelling epidural catheters, hypersensitivity to dabigatran etexilate or to any of the excipients, active clinically significant bleeding, organic lesion at risk of bleeding, spontaneous or pharmacological impairment of haemostasis except for the above included patients groups, concomitant treatment with quinidine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Major Bleeding Events (MBE) During Treatment Period | From first intake (day of surgery) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa | Major bleeding events were defined according to the modified McMaster criteria, and were classified by the investigator as Major bleeding event or Any bleeding event. The criteria for MBE's were: 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 |
| Percentage of Patients With Symptomatic Venous Thromboembolic Events (sVTE) and All Cause Mortality | From first intake (day of surgery) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa | The co-primary efficacy variable sVTE was defined as the composite of documented symptomatic proximal and distal deep vein thrombosis (DVT) and documented symptomatic non-fatal pulmonary embolism (PE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Major Extra-surgical Site Bleedings | From first intake (day of surgery) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa | — |
| Volume of Wound Drainage (Post-operative) | From end of surgery (before first dosing) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa | Total volume of wound drainage is calculated as sum of volume drainage from end of surgery until first dose of Pradaxa plus volume drainage from first dose of Pradaxa and onwards. |
| Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality | From first intake (day of surgery) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa | — |
Countries
Austria, France, Germany, Ireland, Italy, Poland, Spain, Sweden, United Kingdom
Participant flow
Recruitment details
There were 5438 patients enrolled, 5292 were treated. Treated patients are presented.
Pre-assignment details
Phase IV, open-label, prospective, observational, single-arm study on surgery patients (hip and knee surgery)
Participants by arm
| Arm | Count |
|---|---|
| All Patients treated with dabigatran etexilate (Pradaxa), planned dose: 110 mg at the day of surgery, from the day after surgery to last treatment day 220 mg once daily. | 5,292 |
| Total | 5,292 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 270 |
| Overall Study | Lost to Follow-up | 94 |
| Overall Study | Non compliant with European label | 7 |
| Overall Study | No prescription after hospital discharge | 56 |
| Overall Study | Other | 60 |
| Overall Study | Switch to other anticoagulants | 89 |
| Overall Study | Withdrawal by Subject | 56 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age Continuous | 62.6 Years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 3061 Participants |
| Sex: Female, Male Male | 2231 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 5,292 |
| serious Total, serious adverse events | 135 / 5,292 |
Outcome results
Primary
Percentage of Patients With Major Bleeding Events (MBE) During Treatment Period
Major bleeding events were defined according to the modified McMaster criteria, and were classified by the investigator as Major bleeding event or Any bleeding event. The criteria for MBE's were: 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
Time frame: From first intake (day of surgery) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa
Population: Treated Set (TS) comprises all patients who completed the surgery and received at least 1 dose of dabigatran etexilate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Percentage of Patients With Major Bleeding Events (MBE) During Treatment Period | 0.72 Percentage of participants |
Primary
Percentage of Patients With Symptomatic Venous Thromboembolic Events (sVTE) and All Cause Mortality
The co-primary efficacy variable sVTE was defined as the composite of documented symptomatic proximal and distal deep vein thrombosis (DVT) and documented symptomatic non-fatal pulmonary embolism (PE).
Time frame: From first intake (day of surgery) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa
Population: TS
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| All Patients | Percentage of Patients With Symptomatic Venous Thromboembolic Events (sVTE) and All Cause Mortality | 1.04 Percentage of participants | 95% Confidence Interval 0.78 |
Secondary
Percentage of Patients With Major Extra-surgical Site Bleedings
Time frame: From first intake (day of surgery) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa
Population: TS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Percentage of Patients With Major Extra-surgical Site Bleedings | 0.32 Percentage of participants |
Secondary
Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality
Time frame: From first intake (day of surgery) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality | Documented symptomatic proximal DVT | 0.17 Percentage of participants |
| All Patients | Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality | Documented symptomatic distal DVT | 0.87 Percentage of participants |
| All Patients | Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality | Documented symptomatic non-fatal PE | 0.09 Percentage of participants |
| All Patients | Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality | All-cause mortality | 0.06 Percentage of participants |
Secondary
Volume of Wound Drainage (Post-operative)
Total volume of wound drainage is calculated as sum of volume drainage from end of surgery until first dose of Pradaxa plus volume drainage from first dose of Pradaxa and onwards.
Time frame: From end of surgery (before first dosing) until 24 hours after last intake (planned: knee replacement: Day 10 after surgery, hip replacement: Day 28-35 after surgery) of Pradaxa
Population: TS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Volume of Wound Drainage (Post-operative) | 704.5 ml | Standard Deviation 418 |