---
title: EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon
nct_id: NCT01119274
overall_status: COMPLETED
phase: PHASE4
sponsor: Utrecht Institute for Pharmaceutical Sciences
study_type: INTERVENTIONAL
primary_condition: Venous Thromboembolism (VTE)
countries: Austria, Germany, Netherlands
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT01119274.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT01119274"
ct_last_update_post_date: 2013-06-18
last_seen_at: "2026-05-12T06:05:13.285Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon

**NCT ID:** [NCT01119274](https://clinicaltrials.gov/study/NCT01119274)

## Key Facts

- **Status:** COMPLETED
- **Phase:** PHASE4
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 970
- **Lead Sponsor:** Utrecht Institute for Pharmaceutical Sciences
- **Collaborators:** Utrecht University, Leiden University Medical Center, Erasmus Medical Center, University of Ulm, Newcastle University, University of Liverpool, LGC Limited, Uppsala University, Democritus University of Thrace, Elisabethinen Hospital
- **Conditions:** Venous Thromboembolism (VTE), Atrial Fibrillation (AF)
- **Start Date:** 2010-11
- **Completion Date:** 2013-04
- **CT.gov Last Update:** 2013-06-18

## Brief Summary

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.

## Eligibility

- **Minimum age:** 18 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
Inclusion Criteria:

* Patients with either venous thromboembolism (VTE) or atrial fibrillation (AF) requiring coumarin therapy for at least 12 weeks and a target INR in the low intensity range (INR range 2-3 in the United Kingdom, Sweden, Germany, Austria and Greece and INR 2.5-3.5 in the Netherlands)
* Age ≥ 18 years
* Ability to attend scheduled visits
* Signed informed consent

Exclusion Criteria:

* Presence of a mechanical heart valve
* Severe cognitive impairment
* Known genotype CYP2C9 or VKORC1 at start of the study
* Previous or current treatment with any coumarin
* Pregnancy or lactation
* Non-eligible subject
```

## Arms

- **Non-genotype-guided dosing algorithm** (ACTIVE_COMPARATOR)
- **Genotype-guided dosing algorithm** (EXPERIMENTAL)

## Interventions

- **Genotype-guided dosing algorithm** (OTHER) — Loading and monitoring dose according to genotype-guided dosing algorithm
- **Non-genotype-guided dosing algorithm** (OTHER) — Loading and monitoring dose according to non-genotype-guided dosing algorithm

## Primary Outcomes

- **Percent time within therapeutic INR range 2-3 during 12 weeks following the initiation of coumarin therapy** _(time frame: 12 weeks)_
- **Number of patients with INR > or = 4.0, which indicates overanticoagulation** _(time frame: 12 weeks)_

## Secondary Outcomes

- **Time 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: Will be assessed after inclusion of all patients)_

## Locations (3)

- Elisabethinen Hospital Linz, Linz, Austria
- University of Ulm, Ulm, Germany
- Utrecht University, Utrecht, Netherlands

## Recent Field Changes (last 30 days)

- `sponsor.collaborators` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `locations.elisabethinen hospital linz|linz||austria` — added _(2026-05-12)_
- `locations.university of ulm|ulm||germany` — added _(2026-05-12)_
- `locations.utrecht university|utrecht||netherlands` — added _(2026-05-12)_

---

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*Source data (authoritative): https://clinicaltrials.gov/study/NCT01119274*  
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