Clinical trial NCT01064362: Hemorrhage Risk Prescribed Arixtra
Official title: Risk of Hemorrhage in Patients Prescribed Arixtra Compared to LMWH
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Thrombosis, Venous
Keywords: Haemorrhage
Thromboprophylaxis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-02-08
Enrollment: 13442
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients age 18 years and older with a primary discharge diagnosis of hip fracture surgery or hospitalization for hip replacement surgery or knee replacement surgery treated with either fondaparinux sodium or LMWH for thrombopropylaxis between January 2003 and September 2008

Brief summary: Arixtra (fondaparinux sodium) was the first selective Factor Xa inhibitor to be marketed. As with all anticoagulants, an important adverse event associated with Arixtra use is haemorrhage. Previous studies using clinical trial and observational data show no difference in the risk of haemorrhage in patients treated with Arixtra compared to (low molecular weight heparins) LMWHs. This study will assess the risk of haemorrhage in major orthopaedic surgery patients (hip fracture surgery and/or hip/knee replacement surgery) treated with either Arixtra or LMWH for thromboprophylaxis and will provide additional observational data from a European country to strengthen the comprehensive review of haemorrhage and the post-marketing safety of Arixtra. All patients age 18 years and older with a primary discharge diagnosis for hip fracture surgery and/or a hospitalization for hip and/or knee replacement surgery from the PHARMO RLS database in the Netherlands are eligible for participation. For study inclusion patients must receive either Arixtra or LMWH as initial in-hospital thromboprophylactic agent and have at least three months in the PHARMO RLS database before cohort entry date. Patients with a history of hospitalization for haemorrhage, renal failure or liver failure in the past 3 months will be excluded. Descriptive statistics, including gender, age, length of treatment, co-morbidities, concomitant medications, and other covariates will be calculated.

Data for this study were obtained from different registers in the PHARMO medical record linkage system (PHARMO RLS) in the Netherlands. The PHARMO medical record linkage system is a population-based patient-centric data tracking system that includes high quality and complete information of patient demographics, drug dispensing, and hospital morbidity records of approximately 2.3 million community-dwelling inhabitants of 48 geo-demographic areas in the Netherlands. The PHARMO registers are linked on a patient level and contain unprecedented accurate and complete information required for the study.

The out patient database contains drug dispensing data in the U-Expo database are encoded according to standards based upon the Z-Index drug database (www.z-index.nl). Therefore, it is possible to identify and classify drug use in time, both on the basis of national and international classification schemes as well as on the basis of individual active ingredients and administration forms. Of each dispensed drug, the Anatomical Therapeutic Chemical (ATC) code, the dispensing date, the prescriber, the prescribed dosage regimen, the dispensed quantity, the cost and the estimated legend duration of use are available.

The hospital pharmacy database comprises hospital pharmacy data collected in a growing number of non-academic hospitals in the Netherlands. Currently, data are collected on patient level for more than one million patients from a representative sample of non-academic hospital pharmacies scattered over the Netherlands. The hospital pharmacy database includes data on in-patient medication orders such as type of drug, dose, and time of administration and duration of use.

The Dutch Medical Register (LMR) is the data source comprising all hospital admissions in the Netherlands (www.prismant.nl). These records include detailed information concerning the primary and secondary discharge diagnoses, diagnostic, surgical and treatment procedures, type and frequency of consultations with medical specialists and dates of hospital admission and discharge. All diagnoses are coded according to the International Classification of Diseases, 9th edition (ICD-9-CM). Currently, data until December 2008 are available.

Detailed description: Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.

Eligibility criteria: Inclusion Criteria:

* Age 18 years and older; Treatment with either Arixtra or LMWH as initial in-hospital thromboprophylactic agent; At least three months history in the PHARMO RLS database before cohort entry date

Exclusion Criteria:

* Hospitalization for haemorrhage, renal failure or liver failure in the 3 months before cohort entry date

Primary outcomes:
measure: Number of Participants With the Indicated Types of Haemorrhages During Hospitalization or Follow-up for Major Orthopaedic Surgery of Lower Limbs (MOSLL)
timeFrame: Follow-up continued until the date of first event, death, end of initial therapy, hospital discharge, end of follow-up in PHARMO RLS, or 60 days after discharge, whichever came first
Secondary outcomes:
measure: Number of Participants With the Indicated Haemorrhages During Hospitalization for Major Orthopaedic Surgery of Lower Limbs (MOSLL)
timeFrame: Follow-up continued until the date of first event, death, end of initial therapy, hospital discharge, end of follow-up in PHARMO RLS, or 60 days after discharge, whichever came first.
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: