A Phase 4 interventional study of Genotype-guided dosing algorithm and Non-genotype-guided dosing algorithm in Venous Thromboembolism and Atrial Fibrillation, sponsored by Utrecht Institute for Pharmaceutical Sciences. Completed at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-06-18.
Sponsored by Utrecht Institute for Pharmaceutical Sciences · Phase 4 and Interventional
Rationale:
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.
3,870 studies on the registry are indexed under Atrial Fibrillation; 924 are open to participants now.
This study's planned enrollment of 970 is above the median of 144 across 2,380 interventional studies indexed under Atrial Fibrillation.
Browse Atrial Fibrillation studies →Utrecht Institute for Pharmaceutical Sciences is the lead sponsor of 11 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Other: Non-genotype-guided dosing algorithm
Other: Genotype-guided dosing algorithm
Loading and monitoring dose according to genotype-guided dosing algorithm
Loading and monitoring dose according to non-genotype-guided dosing algorithm
Percent time within therapeutic INR range 2-3 during 12 weeks following the initiation of coumarin therapy
Time frame: 12 weeks
Time to INR > or = 4.0, which indicates overanticoagulation.
Time frame: 12 weeks
Percent time spent > or = INR 4.0
Time frame: 12 weeks
Percent time spent < or = INR 2, which indicates under-anticoagulation
Time frame: 12 weeks
Time to reach therapeutic INR defined as the time to the first INR within target range, providing that a subsequent INR > or =1 week later is also within target range
Time frame: 12 weeks
Time to reach stable dose defined as INR within target range for a period of at least 3 weeks with <10% change in dose
Time frame: 12 weeks
Time to and number of minor and major bleeding events
Time frame: 12 weeks
Time to and number of thromboembolic events (therapeutic failure)
Time frame: 12 weeks
The incidence of coumarin sensitivity
Time frame: 12 weeks
The incidence of coumarin resistance
Time frame: 12 weeks
Number of coumarin dose adjustments
Time frame: 12 weeks
The clinical utility of the rapid genotyping test developed by LGC
Time frame: 2 years
Quality of life as reported by the patient tested by the EuroQol (EQ)-5D questionnaire
Time frame: 12 weeks
The cost-effectiveness of genotype-guided dosing for each coumarin compared with non-genotype-guided dosing
Time frame: 2 years
Number of patients with INR > or = 4.0, which indicates overanticoagulation
Time frame: 12 weeks
This study is completed, as verified in Jun 2013. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Utrecht Institute for Pharmaceutical Sciences