Clinical trial NCT00586287: Study to Find Out the Appropriate Initial Dose of the Anticoagulant Drug Phenprocoumon
Official title: Prospective Randomized Trial of a Clinical Algorithm to Predict the Loading Dose of Phenprocoumon
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Embolism
Atrial Fibrillation
Hip Replacement Postoperative
Knee Replacement Postoperative
Keywords: Phenprocoumon
Dosing algorithm
loading dose
Lead sponsor: Cantonal Hospital of St. Gallen
Sponsor class: OTHER
First posted: 2008-01-04
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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)

Primary outcomes:
measure: rate of patients with therapeutic INR levels on day six without anticoagulation-related complications during the loading period
timeFrame: after 30 days
Secondary outcomes:
measure: 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
timeFrame: 30 days
Other outcomes:
Locations:
city: St. Gallen
country: Switzerland
facility: Cantonal Hospital St. Gallen
Study officials:
affiliation: Cantonal Hospital St. Gallen, Switzerland
name: Samuel Henz, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: IKCH - Laboratory St. Gallen Switzerland
name: Wolfgang Korte, MD
role: STUDY_DIRECTOR
References:
citation: Good AC, Henz S. A clinical algorithm to predict the loading dose of phenprocoumon. Thromb Res. 2007;120(6):921-5. doi: 10.1016/j.thromres.2007.01.013. Epub 2007 Mar 12. No abstract available.
citation: Caduff Good A, Nobel D, Krahenbuhl S, Geisen C, Henz S. Randomised trial of a clinical dosing algorithm to start anticoagulation with phenprocoumon. Swiss Med Wkly. 2013 Jan 8;143:w13709. doi: 10.4414/smw.2013.13709. eCollection 2013.