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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Orthopaedic Surgery and Renal Impairment
• Intervention / Treatment: Drug: fondaparinux 1.5 mg/day

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

• Study Type: Interventional
• Enrollment (Actual): 451
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Agen, France, 47000
    • GARANGER Thierry
  • Annonay, France, 07100
    • CHARRET Françoise
  • Bayonne, France, 64109
    • BONNEMAISON Julie
  • Bobigny, France, 93009
    • BELLOUCIF Sadek
  • Bordeaux, France, 33000
    • SZTARCK François
  • Caen, France, 14000
    • PEGOIX Michel
  • Clamart, France, 92140
    • AUSSET Sylvain
  • Clermont-ferrand, France, 63000
    • SCHOEFFLER Pierre
  • Dijon, France, 21079
    • LETOURNEAU Bernard
  • La Roche Sur Yon, France, 85016
    • TISSIER Dominique
  • Le Mans, France, 72000
    • LEMANISSIER Denis
  • Lyon, France, 69006
    • CHAMBON Françoise
  • Lyon, France, 69437
    • BEGOU Gérard
  • Montpellier, France, 34295
    • CAPDEVILLA Xavier
  • Nantes, France, 44200
    • PERON Alain
  • Nice, France, 06200
    • GAERTNER Elisabeth
  • Nimes, France, 30029
    • RIPART Jacques
  • Niort, France, 79006
    • CHEVALEREAUD Erick
  • Paris, France, 75013
    • LANGERON Olivier
  • Paris, France, 75014
    • RABUEL Christophe
  • Paris, France, 75679
    • MAZUIRE Elisabeth
  • Poitiers, France, 86035
    • THERY Philippe
  • Reims, France, 51092
    • BARRE Jeanne
  • Rouen, France, 76031
    • LIGNOT Sophie
  • SAINt-ETIENNE, France, 42 055
    • MARTIN
  • Saint-etienne, France, 42013
    • BAYLOT Denis
  • Saint-saulve, France, 59880
    • DUVERGER Daniel
  • Toulouse, France, 31059
    • FUZIER Régis
  • Tours, France, 37044
    • COUVRET Claude

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: MISMETTI Patrick, MD, Chu Saint-Etienne

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: November 7, 2007
• First Submitted That Met QC Criteria: November 7, 2007
• First Posted (Estimate): November 8, 2007

Study Record Updates

• Last Update Posted (Estimate): August 17, 2011
• Last Update Submitted That Met QC Criteria: July 22, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: renal impairment; Arixtra; anti-Xa activity; major orthopaedic surgery; venous thromboembolic events prevention
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Fondaparinux; PENTA
• Other Study ID Numbers: 0701017; 2007-001048-32 (EudraCT Number)