Kidney Failure, AcutePhase 4NCT00286273
Safety and Efficacy of the Use of Regional Anticoagulation With Citrate in Continuous Venovenous Hemofiltration
A Phase 4 study testing trisodium citrate and nadroparin in people with Kidney Failure, Acute, run by Onze Lieve Vrouwe Gasthuis at 1 site in Netherlands.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Failure, Acute
- What is being tested?
- trisodium citrate and nadroparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 215 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2003to Mar 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Intensive care patients scheduled for continuous venovenous hemofiltration
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- trisodium citrate, nadroparin
- Keywords
- kidney failure, acute, venovenous hemofiltration, hemorrhage, heparin, low-molecular-weight, nadroparin, citrates
- Medical subject headings
- Acute Kidney Injury, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
trisodium citrateDrug
Also called regional anticoagulation with citrate
for regional anticoagulation of the extracorporeal CVVH circuit
nadroparinDrug
Also called nadroparin is a low molecular weight heparin
for anticoagulation of the extracorporeal CVVH circuit
| Study group | Role | What they receive |
|---|---|---|
| citrate | Active comparator | regional anticoagulation with citrate Receives: Drug: trisodium citrate |
| nadroparin | Active comparator | nadroparin is a low molecular weight heparin Receives: Drug: nadroparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
bleeding complications
Measured: during administration of study anticoagulant
transfusion requirement
Measured: during administration of study anticoagulant
filter survival
Measured: during hemofiltration
Secondary outcomes (1)
mortality
Measured: 3-month and hospital admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2006 (estimated)
- Study startMar 2003
- Primary completionJan 2008
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Kidney Failure, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 215 participants (actual)
Sponsor and investigators
- Lead sponsor
- Onze Lieve Vrouwe Gasthuis
- Sponsor type
- University, hospital or other
- Investigators
- Heleen M Oudemans-van Straaten, MD,PhD, Principal investigator, Onze Lieve Vrouwe Gasthuis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00286273
- Sponsor's protocol ID
- WON 03.1
- Status last verified
- Aug 2009
- First submitted
- 1 Feb 2006
- Last updated
- 26 Aug 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19114912Tsujimoto 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.
PubMed 33314078
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00286273
- Acronym / sponsor ID
- WON 03.1
- Conditions
- Kidney Failure, Acute
- Keywords
- kidney failure, acute, venovenous hemofiltration, hemorrhage, heparin, low-molecular-weight, nadroparin, citrates
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 215 participants (actual)
- Lead sponsor
- Onze Lieve Vrouwe GasthuisUniversity, hospital or other
- Study start
- Mar 2003
- Primary completion
- Jan 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 3 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| citrate | Active comparator | Drug: trisodium citrateregional anticoagulation with citrate |
| nadroparin | Active comparator | Drug: nadroparinnadroparin is a low molecular weight heparin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Intensive care patients scheduled for continuous venovenous hemofiltration
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| trisodium citrateAlso: regional anticoagulation with citratefor regional anticoagulation of the extracorporeal CVVH circuit | Drug | citrate |
| nadroparinAlso: nadroparin is a low molecular weight heparinfor anticoagulation of the extracorporeal CVVH circuit | Drug | nadroparin |
Primary outcome
bleeding complications
Time frame: during administration of study anticoagulant
transfusion requirement
Time frame: during administration of study anticoagulant
filter survival
Time frame: during hemofiltration
1 secondary outcome
mortality
Time frame: 3-month and hospital admission
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2009.
- Results publication: PubMed 19114912Oudemans-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.
- Derived from this study: PubMed 33314078Tsujimoto 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heleen M Oudemans-van Straaten, MD,PhD principal investigator
Onze Lieve Vrouwe Gasthuis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing trisodium citrate and nadroparin in people with Kidney Failure, Acute, run by Onze Lieve Vrouwe Gasthuis at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
bleeding complications (time frame: during administration of study anticoagulant). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00286273, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2009.