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

Kidney Failure, Acute Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00286273
• Other study ID #: WON 03.1
• Status: Completed
• Phase: Phase 4
• First received: February 1, 2006
• Last updated: August 25, 2009
• Start date: March 2003
• Est. completion date: March 2008

Study information

• Verified date: August 2009
• Source: Onze Lieve Vrouwe Gasthuis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: March 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Kidney Injury
• Kidney Failure, Acute
• Renal Insufficiency

Intervention

Drug:
• trisodium citrate
for regional anticoagulation of the extracorporeal CVVH circuit
• nadroparin
for anticoagulation of the extracorporeal CVVH circuit

Locations

Country	Name	City	State
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Onze Lieve Vrouwe Gasthuis

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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.0b013e318195 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	bleeding complications		during administration of study anticoagulant	Yes
Primary	transfusion requirement		during administration of study anticoagulant	Yes
Primary	filter survival		during hemofiltration	Yes
Secondary	mortality		3-month and hospital admission	Yes