Track topics on Twitter Track topics that are important to you
The narrow therapeutic range and wide inter-patient variability in dose requirement make anticoagulation response to coumarin derivatives unpredictable. As a result, patients require frequent monitoring to avert adverse effects and maintain therapeutic efficacy. Polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) jointly account for about 40% of the inter-individual variability in dose requirements. To date, several pharmacogenetic guided dosing algorithms for coumarin derivatives, predominately for warfarin, have been developed. However, the potential benefit of these dosing algorithms in terms of their safety and clinical utility has not been adequately investigated in randomised settings. Objective:
To determine whether a dosing algorithm containing genetic information increases the time within therapeutic INR range during anticoagulation therapy with each of warfarin, acenocoumarol and phenprocoumon compared to a dosing regimen that does not contain this information. Secondary outcomes of the study include cost effectiveness, number of thromboembolic and bleeding events, time to reach stable dose and number of supratherapeutic INR peaks. Study design: This is a two-armed, single-blinded, randomised controlled trial. In one arm (intervention) patients commencing anticoagulation therapy with either warfarin, acenocoumarol or phenprocoumon will be dosed according to a drug-specific genotype-guided dosing algorithm, which is based on genetic information, clinical data and (in the monitoring phase) previous INR. For the other arm (control) patients will be dosed according to a non-genotype-guided dosing regimen which does not include genetic information. The follow-up period per patient is 3 months. Study population: Newly diagnosed patients of both genders and at least 18 years old who need anticoagulant treatment with either acenocoumarol, phenprocoumon or warfarin within the low intensity INR range will be included in the trial. Main study parameters/endpoints: The % time within therapeutic INR range in the first 3 months of anticoagulation therapy. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Six extra blood samples are taken from each participant at the start of the study. Patients also have to attend 8 scheduled visits within the 3 months study period and are asked to fill in questionnaires. The genotype-guided dosing algorithm is anticipated to improve the accuracy of coumarin dosing and thus improve the safety and efficacy of anticoagulation therapy.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject)
Genotype-guided dosing algorithm, Non-genotype-guided dosing algorithm
Active, not recruiting
Utrecht Institute for Pharmaceutical Sciences
Published on BioPortfolio: 2014-08-27T03:13:52-0400
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...
Determine if a cystatin C-inclusive vancomycin dosing algorithm improved target trough achievement compared to creatinine clearance-guided vancomycin therapy in critically ill patients.
Rationale: The narrow therapeutic range and wide inter-patient variability in dose requirement make anticoagulation response to coumarin derivatives unpredictable. As a result, patients ...
This is a randomized, prospective, open label study to determine the cost-effectiveness of genotype-guided antiplatelet therapy. Patients undergoing percutaneous intervention (PCI) with st...
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 ...
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.
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...
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...
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 ...
The Antivenom Dosing Algorithm specifies the manifestations of Crotalinae (pit viper, formerly known as Crotalidae) snake envenomation that necessitate aggressive management.
Measurable biological parameters that serve for drug development, safety and dosing (DRUG MONITORING).
Tomography using x-ray transmission and a computer algorithm to reconstruct the image.
The genetic constitution of the individual; the characterization of the genes.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The totality of characteristics of reproductive structure, functions, PHENOTYPE, and GENOTYPE, differentiating the MALE from the FEMALE organism.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...