Prospective, Multicentre, Open-label Study Evaluating 1.5 mg/Day of Fondaparinux.

Study Overview
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Brief Summary
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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
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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

Official Title
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Prospective, Multicentre, Open-label Study Evaluating 1.5 mg/Day of Fondaparinux,in Venous Thromboembolic Events Prevention in Patients With Renal Impairment and Undergoing a Major Orthopaedic Surgery. PROPICE Study

Conditions
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Major Orthopaedic Surgery and Renal Impairment

Intervention / Treatment
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* Drug: fondaparinux 1.5 mg/day


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>patients with renal impairment who received Fondaparinux 1.5 mg/l after major orthopaedic surgery | Drug: fondaparinux 1.5 mg/day<br>* Subcutaneous injection of fondaparinux 1.5 mg/l after major orthopaedic surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 10 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 45 day | 
| 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. | 10 days | 
| 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. | at 1 month ± 5 | 
| Death at 1 Month ± 5 Days | Evaluate the total number of death at 1 month ± 5 days | 1 month ± 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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major orthopaedic surgery, venous thromboembolic events prevention, renal impairment, Arixtra, anti-Xa activity