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Sources of the Variability of the Response to Fluindione in Elderly Patients (PREPA)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00313469
First Posted: April 12, 2006
Last Update Posted: August 25, 2011
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Institut National de la Santé Et de la Recherche Médicale, France
GIS Institut de la Longévité
Information provided by (Responsible Party):
France Mentré, Assistance Publique - Hôpitaux de Paris
  Purpose

We propose to study the pharmacokinetic (PK) and pharmacodynamic (PD) components of the response to fluindione, the main oral anticoagulant used in France, in patients over 80.

We expect to gain a better understanding of the role of age, nutritional status, genetic factors and drug interactions in the variability of the response to fluindione.


Condition Phase
Cardiovascular Disease Phase 4

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Sources of the Variability of the Response to Fluindione in Elderly Patients (PREPA) [Etude Des Sources de variabilité de la réponse à la Fluindione Chez Les Personnes âgées de 80 Ans et Plus (PREPA) ]

Further study details as provided by France Mentré, Assistance Publique - Hôpitaux de Paris:

Biospecimen Retention:   Samples With DNA
Blood samples for the measure of drug concentrations Blood samples with DNA measurements

Enrollment: 152
Study Start Date: September 2005
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Detailed Description:

Oral anticoagulant drugs have improved the prognosis of patients with thromboembolic disease. However, optimal oral anticoagulation control is usually hampered by significant interindividual variability coupled with a narrow therapeutic window. In the elderly, this variability is enhanced by concurrent medications, nutritional status and physical condition. Age itself correlates with increased severity of complications, and adverse events due to anticoagulant drug are thought to be responsible for up to 5000 deaths a year in France.

Although half the patients receiving anticoagulant treatment are over 80, there has been only one study targeting this population so far. We therefore propose to study the pharmacokinetic (PK) and pharmacodynamic (PD) components of the response to fluindione, the main oral anticoagulant used in France, in patients over 80.

150 patients beginning fluindione treatment (or resuming after 2 weeks rest) will be recruited in the following departments: Geriatric, Cardiology, Nephrology, Cardiac Surgery, Internal Medicine (CHU Bichat-Claude Bernard, Paris) and Metabolic Diseases and Internal Medicine (CHU d'Angers). Blood sampling will take place before the beginning of the study (J0) to measure baseline INR and coagulation factors II and VII. Fluindione concentrations will also be measured in non-naive patients. INR, coagulation factors and fluindione will be measured at J2, J4, J6, J8, and twice weekly until they leave the hospital or up to a month. Many covariates will be recorded: age, gender, concurrent medications, biochemical analyses, functional and nutritional status. We will also investigate genetic factors by collecting DNA to genotype polymorphisms related to the target of the drug. Recent work has shown that both the response to common anticoagulant drugs and their metabolism was influenced by genetic polymorphisms, and there is now convincing evidence that drug targets are controlled by genetic polymorphisms which can play a major role in the variability of the response.

Throughout the study, the physicians remain free to adapt drug regimen and prescribe additional INR measurements.

Data analysis will be performed in INSERM Unit 738 (CHU Bichat-Claude Bernard) using nonlinear mixed-effect models, statistical techniques allowing the analysis of sparse data while quantifying the sources of variability.

We expect to gain a better understanding of the role of age, nutritional status, genetic factors and drug interactions in the variability of the response to fluindione. We will also assess whether measuring the activity of coagulation factors helps to anticipate dangerous increases in INR. These goals are vital to provide better care of the elderly and minimise costs arising from the frequency of severe side-effects.

Future perspectives include the development of a software and recommendations to help adapt anticoagulant treatment in the elderly, taking into account their condition.

  Eligibility

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Ages Eligible for Study:   80 Years and older   (Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Elderly people (>80 years) initiating a treatment with fluindione
Criteria

Inclusion Criteria:

  • Patients over and including 80 years old
  • Hospitalised in one of the recruiting centers
  • Initiating a treatment with fluindione (either first time or after more than 15 days holidays)

Exclusion Criteria:

  • Contraindication to fluindione or one of its components
  • Patients receiving other medications known to interfere with fluindione and preventing its use
  • Patients with physical or mental impairment preventing them from signing the consent form
  • Patients whose length of stay in hospital is less than 3 days
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00313469


Locations
France
CHU d'Angers
Angers, France, 49000
Hôpital Bichat-Claude Bernard
Paris, France, 75018
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
GIS Institut de la Longévité
Investigators
Principal Investigator: France Mentré, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

Responsible Party: France Mentré, Professor, Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00313469     History of Changes
Other Study ID Numbers: INSERM
GIS Institut Longévité 2003
First Submitted: April 10, 2006
First Posted: April 12, 2006
Last Update Posted: August 25, 2011
Last Verified: August 2011

Keywords provided by France Mentré, Assistance Publique - Hôpitaux de Paris:
Pharmacokinetics/Pharmacodynamics
Elderly
Anticoagulants

Additional relevant MeSH terms:
Cardiovascular Diseases
Fluindione
Anticoagulants