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

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ClinicalTrials.gov Identifier: NCT00313469
Recruitment Status : Completed
First Posted : April 12, 2006
Last Update Posted : August 25, 2011
Sponsor:
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

Tracking Information
First Submitted Date April 10, 2006
First Posted Date April 12, 2006
Last Update Posted Date August 25, 2011
Study Start Date September 2005
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures Not Provided
Original Primary Outcome Measures Not Provided
Change History Complete list of historical versions of study NCT00313469 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Sources of the Variability of the Response to Fluindione in Elderly Patients (PREPA)
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) ]
Brief Summary

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.

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.

Study Type Observational
Study Design Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood samples for the measure of drug concentrations Blood samples with DNA measurements
Sampling Method Non-Probability Sample
Study Population Elderly people (>80 years) initiating a treatment with fluindione
Condition Cardiovascular Disease
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: August 24, 2011)
152
Original Enrollment
 (submitted: April 10, 2006)
150
Actual Study Completion Date April 2008
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 80 Years and older   (Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT00313469
Other Study ID Numbers INSERM
GIS Institut Longévité 2003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party France Mentré, Assistance Publique - Hôpitaux de Paris
Study Sponsor Assistance Publique - Hôpitaux de Paris
Collaborators
  • 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
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date August 2011