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

This study has been completed.
Sponsor:
Information provided by:
Onze Lieve Vrouwe Gasthuis
ClinicalTrials.gov Identifier:
NCT00286273
First received: February 1, 2006
Last updated: August 25, 2009
Last verified: August 2009
  Purpose

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 Intervention Phase
Kidney Failure, Acute
Drug: trisodium citrate
Drug: nadroparin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Onze Lieve Vrouwe Gasthuis:

Primary Outcome Measures:
  • bleeding complications [ Time Frame: during administration of study anticoagulant ] [ Designated as safety issue: Yes ]
  • transfusion requirement [ Time Frame: during administration of study anticoagulant ] [ Designated as safety issue: Yes ]
  • filter survival [ Time Frame: during hemofiltration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • mortality [ Time Frame: 3-month and hospital admission ] [ Designated as safety issue: Yes ]

Enrollment: 215
Study Start Date: March 2003
Study Completion Date: March 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00286273

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:
Responsible Party: HM Oudemans-van Straaten, Onze Lieve Vrouwe Gasthuis
ClinicalTrials.gov Identifier: NCT00286273     History of Changes
Other Study ID Numbers: WON 03.1
Study First Received: February 1, 2006
Last Updated: August 25, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Onze Lieve Vrouwe Gasthuis:
kidney failure, acute
venovenous hemofiltration
hemorrhage
heparin, low-molecular-weight
nadroparin
citrates

Additional relevant MeSH terms:
Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Citric Acid
Dalteparin
Heparin
Heparin, Low-Molecular-Weight
Nadroparin
Anticoagulants
Cardiovascular Agents
Chelating Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sequestering Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014