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

• ClinicalTrials.gov Identifier: NCT00286273
• Recruitment Status: Completed
• First Posted: February 3, 2006
• Last Update Posted: August 26, 2009
• Sponsor: Onze Lieve Vrouwe Gasthuis
• Information provided by: Onze Lieve Vrouwe Gasthuis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Kidney Failure, Acute	Drug: trisodium citrate; Drug: nadroparin	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 215 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of the Use of Regional Anticoagulation With Citrate in Continuous Venovenous Hemofiltration, a Randomized Controlled Trial Comparing Anticoagulation With Citrate to the Low Molecular Weight Heparin Nadroparin
• Study Start Date: March 2003
• Actual Primary Completion Date: January 2008
• Actual Study Completion Date: March 2008

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: citrate; regional anticoagulation with citrate	Drug: trisodium citrate; for regional anticoagulation of the extracorporeal CVVH circuit; Other Name: regional anticoagulation with citrate
Active Comparator: nadroparin; nadroparin is a low molecular weight heparin	Drug: nadroparin; for anticoagulation of the extracorporeal CVVH circuit; Other Name: nadroparin is a low molecular weight heparin

Outcome Measures

Primary Outcome Measures :

1. bleeding complications [ Time Frame: during administration of study anticoagulant ]
2. transfusion requirement [ Time Frame: during administration of study anticoagulant ]
3. filter survival [ Time Frame: during hemofiltration ]

Secondary Outcome Measures :

1. mortality [ Time Frame: 3-month and hospital admission ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands, 1090HM

Sponsors and Collaborators

Onze Lieve Vrouwe Gasthuis

Investigators

• Principal Investigator: Heleen M Oudemans-van Straaten, MD,PhD; Onze Lieve Vrouwe Gasthuis

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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:CD012467. doi: 10.1002/14651858.CD012467.pub3. Review.

• Responsible Party: HM Oudemans-van Straaten, Onze Lieve Vrouwe Gasthuis
• ClinicalTrials.gov Identifier: NCT00286273
• Other Study ID Numbers: WON 03.1
• First Posted: February 3, 2006
• Last Update Posted: August 26, 2009
• Last Verified: August 2009

Keywords provided by Onze Lieve Vrouwe Gasthuis:

kidney failure, acute; venovenous hemofiltration; hemorrhage; heparin, low-molecular-weight; nadroparin; citrates

Additional relevant MeSH terms:

Renal Insufficiency; Acute Kidney Injury; Kidney Diseases; Urologic Diseases; Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Nadroparin; Citric Acid; Sodium Citrate; Anticoagulants; Calcium Chelating Agents; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents