Applying Pharmacogenetic Algorithms to Individualize Dosing of Warfarin

2014-08-27 03:21:12 | BioPortfolio


The purpose of this study is to determine whether DNA analysis improves the efficiency of dosing and safety in patients who are being started on warfarin therapy.Warfarin, a blood thinner (anticoagulant) prescribed to 1-2 million patients in the US, is a leading cause of drug-related adverse events (e.g., severe bleeding), in large part due to dramatic (20-fold) differences between individuals in dose requirements. At least half of this variability now can be explained by 3 common genetic variants, age, body size, and sex; however, warfarin therapy continues to begin with the same dose in every patient with the correct individual dose determined by trial and error. This study proposes to determine genetic variations the same day from DNA simply obtained by swabbing the inside of the cheek and use this information to determine the proper dose regimen individually in each patient. The aim is to show that the investigators can achieve more rapid, efficient, and safe dosing in up to 500-1000 individuals who are initiating warfarin therapy for various clotting disorders across a large healthcare system in order to demonstrate improved dosing effectiveness, efficiency, and safety with genetic-based dosing, which could lead to a nationwide application resulting in as much as a $1 billion dollar annual benefit in healthcare outcomes.


Study Objectives:

The specific objectives of CoumaGen-II to be tested are:

1. To apply routine pharmacogenetic (PG)-guided dosing of warfarin in clinical practice at IHC facilities in the Urban Central Region (i.e., IMC, LDS, AVH), and selected physician offices that are frequent initiators of warfarin) in a major new quality improvement and clinical research initiative.

2. To compare the percentage out-of-range (%OOR) INRs during the first month (and secondarily, 3 months) of warfarin therapy using PG-guided dosing with parallel or historical standard (STD), empiric dosed controls.

3. To compare a modified PG-guided dosing algorithm (mod-IWPC) with a previously generated and validated, multicenter PG-guided algorithm (IWPC).

Study Design:

Qualifying patients being initiated on warfarin therapy with a target INR of 1.5-2.5, 2-3, or 2.5-3.5 will be invited to participate and sign informed consent. Enrolled patients will receive DNA sampling by buccal swab, and samples will be processed and a PG-guided initial dose calculated with a goal of <6 hours (maximum, 24 hours). Dosing and dose adjustments will be managed through the UCR (IMC/LDSH) anticoagulation management service (AMS). Dose adjustments through day 8 will use a PG-modified algorithm, after which modification will revert to the standard IHC algorithm. AMS pharmacists and study coordinators will ascertain warfarin doses, INRs, dose changes, and adverse events, and record information on case report forms.

Study Duration:

Each patient will participate for approximately 3 months (90 days ± 10 days). The anticipated enrollment period is 24 months or until 1000 patients are enrolled. The length of the enrollment period is subject to revision as it is dependent on the availability of a robust patient pool.

Further study details on dosing algorithm and genotyping methodology may be provided by Intermountain Healthcare Inc.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment




IWPC adapted genotype-guided dosing algorithm for warfarin, Modified IWPC genetic-guided warfarin dosing algorithm


Intermountain Healthcare Hospitals and Clinics
Salt Lake City
United States




Intermountain Health Care, Inc.

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:21:12-0400

Clinical Trials [2231 Associated Clinical Trials listed on BioPortfolio]

Clarification of Optimal Anticoagulation Through Genetics

Individuals taking warfarin often need frequent dose changes as the international normalized ratio (INR) gets too high or too low which could result in a higher risk of thromboembolism, bl...

EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin

Rationale: The narrow therapeutic range and wide inter-patient variability in dose requirement make anticoagulation response to coumarin derivatives unpredictable. As a result, patients ...

EUropean Pharmacogenetics of AntiCoagulant Therapy - Acenocoumarol

Rationale: The narrow therapeutic range and wide inter-patient variability in dose requirement make anticoagulation response to coumarin derivatives unpredictable. As a result, patients ...

Prospective Trial of a Validated Algorithm for Warfarin Dosing

The aim of this study is to perform a randomized trial comparing the use of the algorithm, with dosing of warfarin in standard manual dosage clinical practice, in a high quality anticoagul...

Simple Warfarin Dosing Algorithm Study

Can a simple and cost-free tool help family physicians to improve dosing of the blood thinner warfarin? Warfarin is a blood thinner with a variable effect and requires regular blood monit...

PubMed Articles [9333 Associated PubMed Articles listed on BioPortfolio]

Genotype-guided dosing versus conventional dosing of warfarin: A meta-analysis of 15 randomized controlled trials.

Genotype-guided warfarin dosing algorithm is designed to predict the initial and stable dose of warfarin. However, whether this strategy is superior to conventional dosing method has not been consiste...

Genotype-guided Warfarin Dosing in Patients with Mechanical Valves: a Randomized Controlled Trial.

The clinical utility of genotype-guided warfarin dosing remains controversial. The objective of this trial was to evaluate the efficacy and safety of genotype-guided warfarin dosing in East Asians.

Ensemble of machine learning algorithms using the stacked generalization approach to estimate the warfarin dose.

Warfarin dosing remains challenging due to narrow therapeutic index and highly individual variability. Incorrect warfarin dosing is associated with devastating adverse events. Remarkable efforts have ...

Novel Implementation of Genotype-Guided Proton Pump Inhibitor Medication Therapy in Children: A Pilot, Randomized, Multisite Pragmatic Trial.

The efficacy of proton pump inhibitor (PPI) medications is highly dependent on plasma concentrations, which varies considerably due to cytochrome P450 (CYP2C19) genetic variation. We conducted a pragm...

A UGT1A1 genotype-guided dosing study of modified FOLFIRINOX in previously untreated patients with advanced gastrointestinal malignancies.

FOLFIRINOX (5-fluorouracil [5-FU], leucovorin, irinotecan, oxaliplatin) is an effective but toxic therapy for pancreatic cancer. UGT1A1 (UDP glucuronosyltransferase 1A1) eliminates the active metaboli...

Medical and Biotech [MESH] Definitions

An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.

Food derived from genetically modified organisms (ORGANISMS, GENETICALLY MODIFIED).

Analysis based on the mathematical function first formulated by Jean-Baptiste-Joseph Fourier in 1807. The function, known as the Fourier transform, describes the sinusoidal pattern of any fluctuating pattern in the physical world in terms of its amplitude and its phase. It has broad applications in biomedicine, e.g., analysis of the x-ray crystallography data pivotal in identifying the double helical nature of DNA and in analysis of other molecules, including viruses, and the modified back-projection algorithm universally used in computerized tomography imaging, etc. (From Segen, The Dictionary of Modern Medicine, 1992)

Measurable biological parameters that serve for drug development, safety and dosing (DRUG MONITORING).

A coumarin that is used as an anticoagulant. Its actions and uses are similar to those of WARFARIN. (From Martindale, The Extra Pharmacopoeia, 30th ed, p233)

More From BioPortfolio on "Applying Pharmacogenetic Algorithms to Individualize Dosing of Warfarin"

Quick Search


Relevant Topics

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Searches Linking to this Trial