Clinical trial NCT00965328: Nadroparin Anticoagulation for Continuous Venovenous Hemofiltration
Official title: Nadroparin Anticoagulation for Continuous Venovenous Hemofiltration (CVVH), a Randomized Cross-over Trial Comparing Hemostasis Between Two Hemofiltration Rates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney
Acute Renal Failure
Multiple Organ Failure
Keywords: anticoagulation
hemofiltration
acute kidney injury
heparin
hemostasis
nadroparin
anti-Xa
endogenous thrombin potential
Lead sponsor: Onze Lieve Vrouwe Gasthuis
Sponsor class: OTHER
First posted: 2009-08-25
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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

1. whether nadroparin accumulates in plasma
2. whether nadroparin is removed by filtration and whether removal depends on hemofiltration dose
3. the effects of nadroparin during critical illness on coagulation and anticoagulation

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Accumulation of anti-Xa activity in plasma and removal of anti-Xa activity by filtration.
timeFrame: 24 hours
Secondary outcomes:
measure: Endogenous thrombin potential, D-dimers, Prothrombin fragments 1-2, thrombin-antithrombin complexes
timeFrame: 24 hours
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
Study officials:
affiliation: Onze Lieve Vrouwe Gasthuis
name: Heleen Oudemans-van Straaten, MD.PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tsujimoto Y, Miki S, Shimada H, Tsujimoto H, Yasuda H, Kataoka Y, Fujii T. Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2021 Sep 14;9(9):CD013330. doi: 10.1002/14651858.CD013330.pub2.
citation: Tsujimoto H, Tsujimoto Y, Nakata Y, Fujii T, Takahashi S, Akazawa M, Kataoka Y. Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2020 Dec 14;12(12):CD012467. doi: 10.1002/14651858.CD012467.pub3.
citation: Oudemans-van Straaten HM, van Schilfgaarde M, Molenaar PJ, Wester JP, Leyte A. Hemostasis during low molecular weight heparin anticoagulation for continuous venovenous hemofiltration: a randomized cross-over trial comparing two hemofiltration rates. Crit Care. 2009;13(6):R193. doi: 10.1186/cc8191. Epub 2009 Dec 3.