Safety and Efficacy of the Use of Regional Anticoagulation With Citrate in Continuous Venovenous Hemofiltration

NCT ID: NCT00286273

Last Updated: 2009-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 215 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-03-31
• Study Completion Date: 2008-03-31

Brief Summary

Severely ill patients admitted to the intensive care unit may develop an acute failure of kidney function. To bridge the period to recovery, renal function is temporarily replaced by continuous venovenous hemofiltration (CVVH). To prevent clotting of the hemofiltration circuit, heparin is generally used, providing anticoagulation in the circuit and the patient. As a result, bleeding complications may occur, necessitating the transfusion of blood. Anticoagulation of the circuit can also be obtained with the use of tri-sodium citrate, which provides anticoagulation of the circuit without affecting coagulation in the patient and thus without increasing his/her risk of bleeding. The use of citrate may however cause metabolic complications.

Primary aim of the present study is to show in a larger group of intensive care patients whether the use of regional anticoagulation with citrate is safe compared to systemic anticoagulation with the low molecular weight heparin nadroparin.

Detailed Description

Severely ill patients admitted to the intensive care unit may develop an acute failure of kidney function. Renal function generally recovers if the acute illness improves. To bridge this period, renal function is temporarily replaced by continuous hemofiltration, so called continuous venovenous hemofiltration (CVVH). To remove toxic substances and fluids, the patient's blood flows through a circuit, containing a filter. Flow in the filter is regulated by the CVVH-device.

Normally blood starts to clot as soon as it leaves the body. To prevent clotting of the blood in the filter, the blood has to be 'anticoagulated'. For this purpose, heparins are generally used. Heparins make the blood less likely to clot. Drawback of the use of heparins is that they not only prevent clotting of blood in the circuit and the filter, but also in the patient. Heparins thereby increase the risk of bleeding. Intensive care patients are at higher risk of bleeding due to a recent operation or trauma, ulcers in the mouth or the stomach, or abnormalities in their blood to the acute illness. Due to the continuous application of CVVH for days, anticoagulation is administered without interruption over prolonged periods of time. Studies report bleeding complications in 5 to 50% of the patients. As a result of bleeding, patients need blood transfusion and sometimes surgery. Control of bleeding is sometimes extremely difficult.

An alternative to heparin is citrate, which allows regional anticoagulation of the circuit and the filter without an effect increasing the risk of bleeding for the patient. Anticoagulation with citrate is more complex, nurses need to follow a strict protocol.. Several small studies have shown that regional anticoagulation with citrate is associated with less bleeding and a longer filter survival. The use if citrate is however associated with a greater risk of metabolic complications, if the protocol is not strictly followed. Primary aim of the present study is to show in a larger group of intensive care patients whether the use of regional anticoagulation with citrate is safe compared to systemic anticoagulation with the low molecular weight heparin nadroparin.

Conditions

Kidney Failure, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

citrate

regional anticoagulation with citrate

Group Type: ACTIVE_COMPARATOR

trisodium citrate

Intervention Type: DRUG

for regional anticoagulation of the extracorporeal CVVH circuit

nadroparin

nadroparin is a low molecular weight heparin

Group Type: ACTIVE_COMPARATOR

nadroparin

Intervention Type: DRUG

for anticoagulation of the extracorporeal CVVH circuit

Interventions

trisodium citrate

for regional anticoagulation of the extracorporeal CVVH circuit

Intervention Type: DRUG

nadroparin

for anticoagulation of the extracorporeal CVVH circuit

Intervention Type: DRUG

Other Intervention Names

regional anticoagulation with citrate; nadroparin is a low molecular weight heparin

Eligibility Criteria

Inclusion Criteria

• Intensive care patients scheduled for continuous venovenous hemofiltration

Exclusion Criteria

• Severe pre-existent liver failure (cirrhosis Child C), acute liver dysfunction as occurring with septic shock is not a reason for exclusion
• Active bleeding or bleeding necessitating the infusion of two red blood cell units within 24 hours before starting hemofiltration or a fall in hemoglobin of > 0.5 mmol/l. A fall in hemoglobin/hematocrit as a result of fluid loading is not regarded as bleeding.
• Surgery within 24 h prior to CVVH.
• Patients needing full systemic anticoagulation (unfractionated heparin in a dose of > 10000 IU/day, or nadroparin > 3800 IU/day) for other reasons
• Expectation to die within 24 hours
• Chronic dialysis
• Proven or suspected heparin-induced thrombocytopenia

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Onze Lieve Vrouwe Gasthuis

OTHER

Sponsor Role: lead

Responsible Party

Onze Lieve Vrouwe Gasthuis

Principal Investigators

Heleen M Oudemans-van Straaten, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Onze Lieve Vrouwe Gasthuis

Locations

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Countries

Netherlands

References

Oudemans-van Straaten HM, Bosman RJ, Koopmans M, van der Voort PH, Wester JP, van der Spoel JI, Dijksman LM, Zandstra DF. Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med. 2009 Feb;37(2):545-52. doi: 10.1097/CCM.0b013e3181953c5e.

Reference Type: RESULT

PMID: 19114912 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33314078 (View on PubMed)

Other Identifiers

WON 03.1

Identifier Type: -

Identifier Source: org_study_id