Track topics on Twitter Track topics that are important to you
Anticoagulation with warfarin is a common and potentially hazardous therapeutic intervention. It is a leading cause of iatrogenic bleeding events and, hence, of malpractice claims. There are no good alternatives presently for warfarin anticoagulation, and even when alternatives become available (i.e., ximelagatran), cost, labeling, and experience (outcomes-related) issues will continue to favor an extensive and ongoing use of warfarin. If the present study is able to confirm an advantage for a genotype-driven algorithm, in terms of improved efficiency, therapeutic efficacy, and, especially, safety, then a pharmacogenetics approach to warfarin dosing can be recommended as the basis for an Intermountain Health Care (IHC)-wide quality improvement initiative that should improve patient outcomes, reduce resource use (costs of achieving safe and therapeutic anticoagulation), and reduce adverse clinical events. COUMA-GEN is a prospective, randomized study of patients who are to begin chronic warfarin therapy for specific, qualifying clinical reasons (i.e., atrial fibrillation (AF), deep vein thrombosis (DVT), or post-orthopedic surgery prophylaxis). Qualifying patients will be consented and randomized to an individualized, genotype-based warfarin-dosing regimen or to standard care (without knowledge of genotype). In each study arm, a predicted maintenance dose will be determined. All patients will receive a baseline International Normalized Ratio (INR). For patients in all 3 entry strata, a starting dose of warfarin that is twice the assigned daily maintenance dose (according to the specific treatment arm) will be prescribed on the first and second days, and then the dose will revert to the assigned maintenance dose.
The objectives of this study are to determine
1. whether the pharmacogenetic guided arm can maintain patients a greater time in therapeutic range (TTR - percentage of values in the targeted therapeutic range once a therapeutic INR has been established) without clinical adverse events (i.e., bleeding complications or thromboembolic events),
2. whether the pharmacogenetic guided arm can achieve a higher percentage of therapeutic warfarin levels by days 5 and 8 of therapy (without intervening non-study dose adjustment), and
3. whether the pharmacogenetic guided arm can reduce the need for unplanned dose adjustments and additional INR measurements because of excessive (or insufficient) INR level and clinical adverse events, i.e., bleeding complications or thromboembolic events.
The goal is to achieve >75% TTR in the PG-algorithm arm. Compare proportion of patients reaching therapeutic INR on days 5 and 8 and the subsequent and overall proportion ("time") of INR measurements in therapeutic range (TTR) over 3 months between standard and PG-based arms.
This study will enroll 200 qualifying, consenting patients of either gender, 18 years and above, any ethnicity, with life expectancies > 1 year, beginning on chronic outpatient warfarin therapy for AF, or emergency department/outpatient therapy for spontaneous DVT, or inpatient therapy (and continued for 1 mo) after orthopedic surgery for DVT prevention, or heart failure patients (EF<25% or apical akinesis or left ventricular aneurysm or extensive wall motion abnormality) being started on therapy to reduce the risk of thromboembolism.
Allocation: Randomized, Control: Active Control, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Standard of care or genotyping dosing of warfarin dosing
Salt Lake City
Intermountain Health Care, Inc.
Published on BioPortfolio: 2014-08-27T03:44:15-0400
To compare the efficiency and safety between gene-oriented group and standard care group during 90 days of initial warfarin-treatment for requiring anticoagulation patients with valve repl...
Several human genes affect how medications are metabolized by the body. It is believed that knowledge of variations of these genes can help health care providers better manage an anticoagu...
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...
This study compares the clinical effectiveness of a new algorithm (model-based warfarin dosing) with standard practice (doctor's own judgement and intuition) designed to determine the most...
Warfarin (also called Coumadin®) is an anticoagulant drug (blood thinner) given to patients to help prevent blood clots from forming or to help prevent the growth of an existing blood clo...
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.
Data from previous reports, addressing the significance of genotype-guided dosing of warfarin in Egyptian patients, are infrequent and controversial. This study is aimed at demonstrating the validity ...
Previous trials on the effectiveness of genotype-guided warfarin dosing versus conventional dosing have been inconclusive. We conducted a systematic review and meta-analysis of randomized trials compa...
Integrated care for the clinical management of atrial fibrillation patients is advocated as a holistic way to improve outcomes; the simple ABC (Atrial fibrillation Better Care) pathway has been propos...
Warfarin therapy is recommended in children with giant coronary artery aneurysms (GCAAs) after Kawasaki disease (KD). Large individual variability makes it difficult to predict the warfarin dose. Poly...
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.
Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).
Measurable biological parameters that serve for drug development, safety and dosing (DRUG MONITORING).
Long-term changes in the electrophysiological parameters and/or anatomical structures of the HEART ATRIA that result from prolonged changes in atrial rate, often associated with ATRIAL FIBRILLATION or long periods of intense EXERCISE.
A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)