Major Orthopaedic Surgery and Renal Impairment
Conditions
Keywords
major orthopaedic surgery, venous thromboembolic events prevention, renal impairment, Arixtra, anti-Xa activity
Brief summary
Fondaparinux is an antithrombotic agent having already received a regulatory approval by the European Authorities in venous thromboembolic event prevention after major orthopaedic surgery, as total hip replacement (THR), total knee replacement (TKR), hip fracture (HF). The bleeding risk associated with this prescription is highly related to renal function evaluated by creatinin clearance (CrCl). In order to reduce the bleeding risk, it has been proposed to prescribe fondaparinux 1.5 mg/day in patients with a CrCl between 20 and 50ml/mn instead of 2.5mg/day (European MMA). In the meantime, this approval is essentially based on simulated pharmakinetic data without any support of clinical data. prospective, multicentre, open-label study evaluating the safety profile of fondaparinux 1.5 mg/day, subcutaneously administered, in patients with a renal impairment defined by a CrCl between 20 and 30 ml/min and undergoing a major orthopaedic surgery.
Detailed description
Fondaparinux 1.5mg/day subcutaneously administered during post-surgery 1 to 10 days with the 1st treatment administration performed 6 to 8 hours after the end of surgery. Screening visit : \> 7 days before inclusion visit if THR and TKR Inclusion visit : day of surgery Visits with blood drawing: 3 visits scheduled during 1 to 10 days of treatment period Study end of treatment visit: D1 to D10 Study end visit: 1 month ± 15 days
Interventions
DRUGfondaparinux 1.5 mg/day
Subcutaneous injection of fondaparinux 1.5 mg/l after major orthopaedic surgery
Sponsors
GlaxoSmithKline
Centre Hospitalier Universitaire de Saint Etienne
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* • age \> 18 years old, * undergoing a major orthopaedic surgery (THR, TKR, HF) whatever procedure techniques are used, 1st indication or 2nd indication, * requiring an antithrombotic prophylaxis, * presenting a renal impairment defined by a creatinin clearance (CrCl) between 20 and 50 ml/min calculated by Cockcroft and Gault's formula, * having signed the inform consent form.
Exclusion criteria
* contra-indications to fondaparinux, * history of heparin inducted thrombopenia (HIT), * platelets \< 100 g/l.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Major Bleedings Between Day 1 and Day 10. | 10 day | evaluate between Day 1 and Day 10, the number of patients under study treatment who has affected by major bleedings defined as fatal, involved a critical organ, treatment cessation, occurred at the surgical site and necessitated any medical intervention, or if it was overt and necessitated transfusion of \>2 units of packed red blood cells or was associated with a fall in hemoglobin \>20 g/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Major Bleedings at 1 Month ± 5 Days. | 45 day | evaluate the number of patients affected by major bleedings defined as fatal, involved a critical organ, treatment cessation, occurred at the surgical site and necessitated any medical intervention, or if it was overt and necessitated transfusion of \>2 units of packed red blood cells or was associated with a fall in hemoglobin \>20 g/L at 1 month ± 5 days. |
| Number of Patients With Symptomatic Deep Vein Thrombosis and Pumonary Embolism Between Day 1 and Day 10 | 10 days | Evaluate the number of patients affected by symptomatic Deep Vein Thrombosis (any symptomatic distal and/or proximal deep-vein thrombosis) and Pumonary Embolism (symptomatic pulmonary embolism confirmed by objective tests) between Day 1 and Day 10. |
| Number of Patients With Symptomatic Deep Vein Thrombosis and Pumonary Embolism at 1 Month ± 5 Days | at 1 month ± 5 | Evaluate the number of patients affected by symptomatic Deep Vein Thrombosis (any symptomatic distal and/or proximal deep-vein thrombosis) and Pumonary Embolism (symptomatic pulmonary embolism confirmed by objective tests) at 1 month ± 5 days. |
| Death at 1 Month ± 5 Days | 1 month ± 5 days | Evaluate the total number of death at 1 month ± 5 days |
Countries
France
Participant flow
Recruitment details
patients have been included between june 2007 and june 2008 in public and private French hospitals
Pre-assignment details
Nine patients received no study drug due to immediate postoperative death (n=1), consent withdrawal (n=2), use of another thromboprophylactic agent (n=2), surgery change or cancellation (n=2), and CrCl \>50 mL/min just before surgery (n=2)
Participants by arm
| Arm | Count |
|---|---|
| Fondaparinux 1.5 mg/l patients with renal impairment who received Fondaparinux 1.5 mg/l after major orthopaedic surgery | 442 |
| Total | 442 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 10 Days Post-operative | Death | 4 |
| Between 10 Days and 30 Days Postoperativ | Death | 5 |
Baseline characteristics
| Characteristic | Fondaparinux 1.5 mg/l |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 437 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age Continuous | 81.4 years STANDARD_DEVIATION 6.64 |
| Region of Enrollment France | 442 participants |
| Sex: Female, Male Female | 353 Participants |
| Sex: Female, Male Male | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 442 |
| serious Total, serious adverse events | 32 / 442 |
Outcome results
Primary
Number of Patients With Major Bleedings Between Day 1 and Day 10.
evaluate between Day 1 and Day 10, the number of patients under study treatment who has affected by major bleedings defined as fatal, involved a critical organ, treatment cessation, occurred at the surgical site and necessitated any medical intervention, or if it was overt and necessitated transfusion of \>2 units of packed red blood cells or was associated with a fall in hemoglobin \>20 g/L.
Time frame: 10 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fondaparinux 1.5 mg/l | Number of Patients With Major Bleedings Between Day 1 and Day 10. | 20 participants |
Secondary
Death at 1 Month ± 5 Days
Evaluate the total number of death at 1 month ± 5 days
Time frame: 1 month ± 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fondaparinux 1.5 mg/l | Death at 1 Month ± 5 Days | 10 participants |
Secondary
Number of Patients With Major Bleedings at 1 Month ± 5 Days.
evaluate the number of patients affected by major bleedings defined as fatal, involved a critical organ, treatment cessation, occurred at the surgical site and necessitated any medical intervention, or if it was overt and necessitated transfusion of \>2 units of packed red blood cells or was associated with a fall in hemoglobin \>20 g/L at 1 month ± 5 days.
Time frame: 45 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fondaparinux 1.5 mg/l | Number of Patients With Major Bleedings at 1 Month ± 5 Days. | 23 participants |
Secondary
Number of Patients With Symptomatic Deep Vein Thrombosis and Pumonary Embolism at 1 Month ± 5 Days
Evaluate the number of patients affected by symptomatic Deep Vein Thrombosis (any symptomatic distal and/or proximal deep-vein thrombosis) and Pumonary Embolism (symptomatic pulmonary embolism confirmed by objective tests) at 1 month ± 5 days.
Time frame: at 1 month ± 5
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fondaparinux 1.5 mg/l | Number of Patients With Symptomatic Deep Vein Thrombosis and Pumonary Embolism at 1 Month ± 5 Days | 3 participants |
Secondary
Number of Patients With Symptomatic Deep Vein Thrombosis and Pumonary Embolism Between Day 1 and Day 10
Evaluate the number of patients affected by symptomatic Deep Vein Thrombosis (any symptomatic distal and/or proximal deep-vein thrombosis) and Pumonary Embolism (symptomatic pulmonary embolism confirmed by objective tests) between Day 1 and Day 10.
Time frame: 10 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fondaparinux 1.5 mg/l | Number of Patients With Symptomatic Deep Vein Thrombosis and Pumonary Embolism Between Day 1 and Day 10 | 2 participants |