Nadroparin Anticoagulation for Continuous Venovenous Hemofiltration

Study Overview
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Brief Summary
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The low molecular weight heparin nadroparin is used for anticoagulation of the extracorporeal hemofiltration circuit. Continuous hemofiltration is a renal replacement modality for intensive care patients with acute renal failure. Up to now it is not known whether nadroparin is removed by hemofiltration or not. Accumulation would increase the risk of bleeding. Aim of the present study is to determine whether nadroparin accumulates in plasma whether nadroparin is removed by filtration and whether removal depends on hemofiltration dose the effects of nadroparin during critical illness on coagulation and anticoagulation

Detailed Description
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The low molecular weight heparin (LMWH) nadroparin is used for anticoagulation of the extracorporeal hemofiltration circuit. LMWH accumulate in patients with chronic renal failure. Continuous venovenous hemofiltration (CVVH) is a renal replacement modality for intensive care patients with acute renal failure. Up to now it is not known whether nadroparin is removed by hemofiltration or not. If not, accumulation is expected and the risk of bleeding for the patient increases. Because critically ill patients are at increased risk of bleeding, this question is crucial. If nadroparin would be removed by filtration, removal is expected to depend on hemofiltration dose (to be greater with a higher dose) We therefore designed a randomized controlled cross-over trial in the setting of critical illness and acute renal failure comparing the anticoagulant effect of nadroparin (anti-Xa) between two doses of CVVH in the patients blood, in the extracorporeal circuit and in the ultrafiltrate. Because hemostasis in critically ill patients is not only influenced by anticoagulation but also by the critical illness and the extracorporeal circuit, we also measure other hemostatic markers, especially the endogenous thrombin potential (ETP), which seems the most global marker of hemostasis, incorporating procoagulant and anticoagulant effects.

Official Title
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Nadroparin Anticoagulation for Continuous Venovenous Hemofiltration (CVVH), a Randomized Cross-over Trial Comparing Hemostasis Between Two Hemofiltration Rates

Conditions
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Kidney, Acute Renal Failure, Multiple Organ Failure

Intervention / Treatment
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* Procedure: CVVH 4 to 2 L/h
* Procedure: CVVH 2 to 4L/h


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute renal failure requiring renal replacement therapy Exclusion Criteria: (recent) bleeding or a suspicion of bleeding necessitating transfusion, need of therapeutic anticoagulation or (suspected) heparin-induced thrombocytopenia

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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: hemofiltration at 4L/h<br>Hemofiltration was started at 4L/h and crossed over to 2L/h after 60 minutes of hemofiltration | Procedure: CVVH 4 to 2 L/h<br>* CVVH is initiated at 4L/h and is converted to 2L/h after 60 min<br>* Other names: continuous venovenous hemofiltration;|
| Active Comparator: hemofiltration at 2L/h<br>hemofiltration was started at 2L/h and crossed over to 4L/h after 60 min | Procedure: CVVH 2 to 4L/h<br>* CVVH is initiated at 2L/h and is converted to 4L/h after 60 min<br>* Other names: continous venovenous hemofiltration;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accumulation of anti-Xa activity in plasma and removal of anti-Xa activity by filtration. |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endogenous thrombin potential, D-dimers, Prothrombin fragments 1-2, thrombin-antithrombin complexes |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anticoagulation, hemofiltration, acute kidney injury, heparin, hemostasis, nadroparin, anti-Xa, endogenous thrombin potential