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Personalized Warfarin Dosing by Genomics and Computational Intelligence

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ClinicalTrials.gov Identifier: NCT00872079
Recruitment Status : Terminated (Lack of Funding)
First Posted : March 31, 2009
Results First Posted : February 24, 2014
Last Update Posted : February 24, 2014
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Tracking Information
First Submitted Date  ICMJE March 27, 2009
First Posted Date  ICMJE March 31, 2009
Results First Submitted Date  ICMJE February 21, 2014
Results First Posted Date  ICMJE February 24, 2014
Last Update Posted Date February 24, 2014
Study Start Date  ICMJE September 2008
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2014)
Patient Genomics [ Time Frame: Baseline ]
During Aim 2, Determined Patient Genotypes: CYP2C9 and VKORC1.
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2009)
Percent of patients acheiving target INR [ Time Frame: 6 months ]
Change History Complete list of historical versions of study NCT00872079 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Personalized Warfarin Dosing by Genomics and Computational Intelligence
Official Title  ICMJE Personalized Warfarin Dosing Using Genomics and Computational Intelligence
Brief Summary This study will create a computer program that can be used to help dose a drug called warfarin for the prevention of blood clotting. The study will collected specific information about those patients receiving this drug and use that information to create a computer program that will predict the effects of the drug. With this prediction program in place, the investigators can perform a series of "what if I gave this amount of drug" simulations to determine the best dose of drug for that patient. Once the computer programs are developed, the investigators will test the program in patients that actually need this drug. They will also include genetic information into the prediction since it has been shown that this information can affect how well the drug works. Patients will have this genetic information determined during this study.
Detailed Description

The objective of this project is to develop new techniques to incorporate genomic data into pharmacodynamic models to improve the dosing of chronically administered drugs. Specifically, the investigators look to improve warfarin therapy by decreasing the variability in the effect of this drug using information about the subjects genotype and computational intelligence. The investigators propose to achieve our objectives using a prospective, randomized, controlled clinical trial of a computer program that they will develop from both historical and prospective data. This computer program will be tested against a control group using standard warfarin dosing, and a group using standard dosing plus subject genotype. Warfarin dose and response data will be obtained from patients seen in the Louisville VA anticoagulation clinic. Following informed consent, subject genotype for cytochrome P450 allele 2C9 (2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) will be determined. Other data routinely obtained to aid in warfarin dosing will also be recorded. Using this information, the investigators will develop many different models for warfarin dosing using incrementally more information. Each of these models will be tested using computer simulation until they have obtained the best model. This model will be used in a pilot study to test performance in real time. The results of the pilot study will then be used to power a final clinical trial of standard dosing, standard dosing and genetic information, computer dosing, and computer dosing plus genetic information.

The specific aims of this research are:

  1. Determine the structure and the type of neural network model for predictions from historically obtained data. (Computer Model)
  2. Prospectively develop an individualized neural network and nonlinear mixed effect modelling (NONMEM) model capable of predicting erythropoietin dosing for chronic in-center hemodialysis patients using adaptive techniques.
  3. Develop computer programs based on neural computing that can be used in a clinical setting. (Computer Model)
  4. Determine the utility of the computer programs prospectively in the clinical setting.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Condition  ICMJE
  • Venous Thrombosis
  • Atrial Fibrillation
  • Myocardial Infarction
Intervention  ICMJE Device: Genomics
Model predictive control is a computer based algorithm that can be applied to drug dosing. This computer tool uses a model of how a patient will respond to a drug dose based on demographic and historical dosing information to predict a new drug response. A drug dose controller applies all possible doses to the response model and selects the one dose that best meets the stated goals of the drug therapy. In the case of warfarin, we will calculate an international normalized ratio (INR) value within a specific target range.
Study Arms  ICMJE Active Comparator: Genomics

Aim 1: Collect historical data on warfarin dosing in subjects at the VA. Aim 2: Collect genotype information on up to 300 subjects receiving warfarin anticoagulation.

Aim 3: Develop a computer model incorporating the information from Aim 1 and 2. Aim 4: Conduct randomized clinical trial.

Intervention: Device: Genomics
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  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 15, 2010)
175
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2009)
300
Actual Study Completion Date  ICMJE September 2011
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Warfarin therapy
  • Attend anticoagulation clinic
  • Warfarin therapy for 6 months

Exclusion Criteria:

  • History of non-compliance
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00872079
Other Study ID Numbers  ICMJE CAMM-04-07S
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party VA Office of Research and Development ( US Department of Veterans Affairs )
Study Sponsor  ICMJE US Department of Veterans Affairs
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael E. Brier, PhD VA Medical Center, Louisville
PRS Account VA Office of Research and Development
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP