Pharmacokinetics of Fondaparinux in Patients With Major Orthopedic Surgery (POP-A-RIX)

Population Pharmacokinetics of Fondaparinux Administered at Prophylactic Doses After Major Orthopedic Surgery in Everyday Practice

Fondaparinux is a synthetic antithrombotic agent with specific anti-factor Xa activity. A population pharmacokinetic model of fondaparinux, based on data obtained in patients included in phase II/III trials, has been described. However, the validity of this model in everyday practice needed to be confirmed. This study was a multicenter, prospective cohort study in consecutive orthopedic patients treated with 2.5 mg of fondaparinux. Anti-Xa activities were recorded in 809 patients. Population parameters and inter-individual variability were estimated using NONMEM VI software. A two-compartment model with first-order absorption best described fondaparinux pharmacokinetics. Covariates partly explaining inter-individual variability were body weight, age and creatinine clearance estimated by the simplified Modification of Diet in Renal Disease formula. A body weight less than 50 kg and moderate renal failure increased drug exposure. These results suggest that fondaparinux pharmacokinetics need to be confirmed in patient populations not fully assessed in phase II/III studies

Study Overview

• Status: Completed
• Conditions: Orthopedic Surgery

• Study Type: Observational
• Enrollment (Actual): 997

Contacts and Locations

Study Locations

• France
  • Annonay, France, 07100
    • CHARRET Françoise
  • Caen, France, 14000
    • PEGOIX Michel
  • Paris, France, 75679
    • ROSENCHER Nadia
  • Pierre Bénite, France, 69495
    • PETIT Pierre-Yves
  • Reims, France, 51092
    • BARRE Jeanne
  • Rouen, France, 76031
    • MAITRE Anne-Marie
  • Saint-etienne, France, 42013
    • BAYLOT Denis
  • Saint-etienne, France, 42100
    • ZUFFEREY Paul

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with major orthopedic surgery who need prophylactic doses of fondaprinux

Description

Inclusion Criteria:

• patient who need leg major orthopedic surgery
• age > 18 years
• patient who need prophylactic doses of fondaparinux

Exclusion Criteria:

• contra-indication to fondaparinux
• renal insufficiency

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
patients with blood sample; Patients with major orthopedic surgery and prophylactic doses of fondaparinux who have 3 blood sample during their hospitalization to measure anti-Xa activity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine an anti-Xa activity value which is predicted of a haemorrhage risk	day 9

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: February 4, 2010
• First Submitted That Met QC Criteria: February 4, 2010
• First Posted (Estimate): February 5, 2010

Study Record Updates

• Last Update Posted (Estimate): February 5, 2010
• Last Update Submitted That Met QC Criteria: February 4, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: orthopedic surgery; fondaparinux; patients with major orthopedic surgery
• Other Study ID Numbers: 0601069