Pharmacokinetics of Dalteparin in Patients With Impaired Renal Function

Study Overview
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Brief Summary
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Low molecular weight heparins (LMWH) have been shown to be at least as efficient and safe as unfractioned heparin (UFH) in prophylaxis and treatment of venous thromboembolic events and in therapy of acute cardiovascular diseases. LMWH are widely used as safe replacement of oral anticoagulation with vitamin K antagonists (VKA). Due to their pharmacokinetic characteristics, LMWH tend to accumulate in patients with impaired renal function. Official guidelines recommend therefore to use LMWH controlled by Anti-Xa levels or to use UFH instead of LMWH to provide full therapeutic anticoagulation therapy in patients with severe renal insufficiency. Although dosage recommendations have been proposed for enoxaparin in patients with renal impairment based on several studies, these data cannot be applied to other LMWH directly due to different pharmacokinetic properties of each drug. The present study aims to clarify the pharmacokinetics of dalteparin in patients with renal insufficiency, especially addressing the question of accumulation after multiple doses and including patients with severe renal insufficiency and derive a safe and suitable concept for using dalteparin in patients with impaired renal function.

Official Title
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Pharmacokinetics of Dalteparin in Patients With Impaired Renal Function

Conditions
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Renal Insufficiency

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient starting with dalteparin for prophylaxis OR therapy by order of the treating physician (after having evaluated clinical indication and contraindications). Renal function normal OR impaired with or without dialysis therapy according to open study groups Age >= 18 years Written informed consent Exclusion Criteria: Pregnancy / Lactation Dalteparin or other LMWH already in use for > 1 day, unless just in use during hemodialysis Anti-Xa level before first application of dalteparin > 0.3 U / ml Participation in another study Anuria OR glomerular filtration rate < 10 ml/min without dialysis Patient on intensive care unit (ICU) Cardiovascular unstable patient or probable need for a quick stop of anticoagulation (e.g. emergency surgery) Patient with a disease whose estimated life expectancy is < 28 days

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| P - A<br>Prophylactic Dosage, GFR >= 60 mL/min/1.73m^2 | |
| P - B<br>Prophylactic Dosage, GFR 30-59 mL/min/1.73m^2 | |
| P - C<br>Prophylactic Dosage, GFR < 30 mL/min/1.73m^2 | |
| P - CAPD<br>Prophylactic Dosage, CAPD | |
| T - A<br>Therapeutic Dosage, GFR >= 60 mL/min/1.73m^2 | |
| T - B<br>Therapeutic Dosage, GFR 30-59 mL/min/1.73m^2 | |
| T - C<br>Therapeutic Dosage, GFR < 30 mL/min/1.73m^2 | |
| T - CAPD<br>Therapeutic Dosage, CAPD | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |