Study to Find Out the Appropriate Initial Dose of the Anticoagulant Drug Phenprocoumon

Study Overview
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Brief Summary
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Oral anticoagulation is often initiated in hospitalized patients. Although the therapeutic range of phenprocoumon is narrow, the individual drug demands unfortunately vary greatly between persons. Our group recently developed two dosing algorithms for the initiation of anticoagulation based on clinical predictors such as age, gender, body weight and laboratory values. The aim of the proposed study is to prospectively evaluate the efficacy and safety of these two algorithms in medical and orthopedic inpatients, as well as in a group of outpatients and possibly in a geriatric collective.

Detailed Description
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Background: The presently available oral anticoagulants have a very narrow therapeutic range but the interindividual demands to achieve therapeutic anticoagulation (=loading dose) varies greatly. Overanticoagulation is a major cause of bleeding complications, whereas insufficient anticoagulation is associated with thromboembolic disease and possibly prolonged hospital stay. A model to predict the loading dose with phenprocoumon (Marcoumar®) is therefore highly desirable. In a retrospective analysis of 300 inpatients (152 medical, 148 orthopedic patients) of the Cantonal Hospital of St. Gallen our group identified clinical predictors for the loading dose of phenprocoumon and two dosing algorithms were developed (Good AC, Henz S. A clinical algorithm to predict the loading dose of phenprocoumon. Thromb Res. 2007;120(6):921-5.). In order to validate the safety and efficacy of these dosing algorithms we plan this prospective interventional study with three equally sized arms: dosing according to algorithm 1, dosing according to algorithm 2 or dosing according to the estimate of the physician (control).

Official Title
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Prospective Randomized Trial of a Clinical Algorithm to Predict the Loading Dose of Phenprocoumon

Conditions
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Pulmonary Embolism, Atrial Fibrillation, Hip Replacement Postoperative, Knee Replacement Postoperative

Intervention / Treatment
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* Other: Algorithm for phenprocoumon
* Other: algorithm for phenprocoumon
* Drug: Phenprocoumon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive inpatients of the internal medicine and the orthopedic surgery department of the Cantonal Hospital of St. Gallen needing new onset oral anticoagulation Exclusion Criteria: Patients with prior oral anticoagulation with coumarines within less than 6 weeks, patents, who received vitamin-K supplements within less than one week before the onset of oral anticoagulation, patients with liver cirrhosis other than Child A, pregnant women (pregnancy has to be excluded in women of childbearing age), patients younger than 18 years, and patients unwilling or unable to give informed consent patients with (clinically diagnosed) dementia and persons with insufficient German, French, Italian or English language skills)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Algorithm which uses serum albumin and weight to determine the loading dose of phenprocoumon within the first 5 days | Other: Algorithm for phenprocoumon<br>* Dosing of phenprocoumon for days 1 to 3, measuring INR and adjust dose according algorithm A published in (Good AC, Henz S. A clinical algorithm to predict the loading dose of phenprocoumon. Thromb Res. 2007;120(6):921-5.)<br>* Other names: Marcoumar;|
| Experimental: B<br>Algorithm which uses serum age and weight to determine the loading dose of phenprocoumon within the first 5 days | Other: algorithm for phenprocoumon<br>* Dosing of phenprocoumon for days 1 to 3, measuring INR and adjust dose according algorithm B published in (Good AC, Henz S. A clinical algorithm to predict the loading dose of phenprocoumon. Thromb Res. 2007;120(6):921-5.)<br>* Other names: Marcoumar;|
| Active Comparator: C<br>The physician chooses the loading dose of phenprocoumon according to his/her experience | Drug: Phenprocoumon<br>* Dosing of phenprocoumon for days 1 to 3, measuring INR and adjust dose according to the discretion of the treating physician<br>* Other names: Marcoumar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of patients with therapeutic INR levels on day six without anticoagulation-related complications during the loading period |  | after 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the time-course of the INR-values, the rate of excessive INR-values, defined as INR >3.5 within 10 days, the rate of minor and major bleeding complications, the length of stay, and death within 30 days |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phenprocoumon, Dosing algorithm, loading dose