Ignite Creation Date:
2024-05-05 @ 12:00 PM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00209378
Status:
COMPLETED
Last Update Posted:
2013-04-04
First Post:
2005-09-13
Brief Title:
Citrate Versus Heparin Anticoagulation in Continuous Venovenous Hemofiltration
Sponsor:
Free University Medical Center
Organization:
Free University Medical Center
Study Overview
Official Title:
Citrate Versus Heparin Anticoagulation in Continuous Venovenous Hemofiltration in Critically Ill Patients With Acute Renal Failure A Randomized Clinical Trial
Status:
COMPLETED
Status Verified Date:
2013-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CASH-CVVH
Brief Summary:
The purpose of this study is to compare citrate regional anticoagulation with systemic heparinization in continuous venovenous hemofiltration The investigators hypothesis is that regional citrate anticoagulation with replacement solution containing trisodium citrate will be associated with lower mortality and less bleeding complications compared to heparin with also a better filter survival
Detailed Description:
Acute renal failure occurs in about 20 of critically ill patients and is associated with increased morbidity and mortality in spite of modern renal replacement techniques The latter include continuous venovenous hemofiltration CVVH techniques necessitating anticoagulation of blood entering the extracorporeal circuit to prevent premature clot formation and hemofilter dysfunction Heparin is commonly used for that purpose but carries a serious risk of bleeding complications and heparin induced thrombocytopenia In a subgroup of critically ill patients systemic anticoagulation is absolutely contraindicated Citrate-anticoagulant CVVH carries the potential advantage of less bleeding complications and prolonged filter survival but carries the risk of hypocalcaemia when citrate is inappropriately or insufficiently counteracted by calcium infusion after passage of blood through the filter In addition when too much citrate enters the circulation a metabolic alkalosis may develop since citrate is converted to bicarbonate by the liver
Moreover continuous filtration techniques may attenuate a potentially harmful exaggerated immune response particularly when high volume filtration 6 Lh is used Also the type of anticoagulation may modulate immune responses as known from biocompatibility studies in intermittent hemodialysis
In the first part of the research proposal concerning high bleeding risk patients a comparison will be made in a prospective sequential cohort study between no anticoagulation and citrate regarding filter survival time bleeding risk dialyser efficacy circulating immune mediators such as neutrophil elastase and myeloperoxidase interleukins platelet-activating factors activated complement products soluble cytokine receptors and adhesion molecules metabolic balance and acute renal failure duration Also filter survival time will be assessed The purpose of the second part of the current research proposal is to evaluate in a randomised controlled clinical trial in 350 critically ill patients 18-80 years with acute renal failure 2 arms of 175 patients without an increased bleeding risk thrombocytes 40 x 109L APTT 60 sec PT-INR 2 whether citrate CVVH is better than bicarbonate-heparin CVVH in terms of the same parameters as in the first part of the study but with the addition of mortality as the primary endpoint
For this purpose a simple predilution system and citrate adjustment protocol will be used and compared to standard heparin dosing This replacement solution shall be custom made containing trisodium citrate no lactate or bicarbonate no calcium and a low sodium content
Main objective Investigation of the mortality during continuous venovenous hemofiltration with systemic anticoagulation with heparin compared with regional anticoagulation with trisodium citrate and also the investigation of the filter survival Our hypothesis is that regional citrate anticoagulation with replacement solution containing trisodium citrate will be associated with less bleeding complications compared to heparin with also a better filter survival Most important we want to evaluate the hypothesis that treatment with citrate will result in a lower mortality compared to treatment with systemic heparinization
Regional anticoagulation with trisodium citrate may also have some potential effects on the immune response as known from biocompatibility studies in intermittent hemodialysis Bioincompatibility leads to polymorphonuclear cell degranulation as indicated by the release of intracellular granule products such as myeloperoxidase lactoferrin lysozyme and elastase Citrate anticoagulation may lead to a lower polymorphonuclear cell degranulation since cations play a pivotal role in the process of cell activation and citrate creates an almost calcium-free environment within the dialyser by its virtue to chelate calcium
Primary endpoints
Mortality at day 28 after inclusion will be evaluated Survival time of the first hemofilter used will be determined including the cause of filter termination and the number of filters used in the first 72 hours the average filter patency time will be calculated
Citrate CVVH is stopped and thus also the study if the patient fulfils one of the following criteria
1 Total to ionised calcium ratio of more than 25
2 Persistent metabolic alkalosis with a BE of more than 10
3 Clinical signs of hypocalcaemia tetanic symptoms or prolonged QT interval
4 Progressive non-lactic acidosis pH 720 during CVVH combined with an increase in anion gap 13 without the presence of endo- or exogenous acids other than citrate suggesting citrate accumulation
Patients on heparin developing a HIT will continue CVVH with danaparoid anticoagulation Patients on heparin developing a bleeding episode will continue CVVH with regional citrate anticoagulation
Moreover continuous filtration techniques may attenuate a potentially harmful exaggerated immune response particularly when high volume filtration 6 Lh is used Also the type of anticoagulation may modulate immune responses as known from biocompatibility studies in intermittent hemodialysis
In the first part of the research proposal concerning high bleeding risk patients a comparison will be made in a prospective sequential cohort study between no anticoagulation and citrate regarding filter survival time bleeding risk dialyser efficacy circulating immune mediators such as neutrophil elastase and myeloperoxidase interleukins platelet-activating factors activated complement products soluble cytokine receptors and adhesion molecules metabolic balance and acute renal failure duration Also filter survival time will be assessed The purpose of the second part of the current research proposal is to evaluate in a randomised controlled clinical trial in 350 critically ill patients 18-80 years with acute renal failure 2 arms of 175 patients without an increased bleeding risk thrombocytes 40 x 109L APTT 60 sec PT-INR 2 whether citrate CVVH is better than bicarbonate-heparin CVVH in terms of the same parameters as in the first part of the study but with the addition of mortality as the primary endpoint
For this purpose a simple predilution system and citrate adjustment protocol will be used and compared to standard heparin dosing This replacement solution shall be custom made containing trisodium citrate no lactate or bicarbonate no calcium and a low sodium content
Main objective Investigation of the mortality during continuous venovenous hemofiltration with systemic anticoagulation with heparin compared with regional anticoagulation with trisodium citrate and also the investigation of the filter survival Our hypothesis is that regional citrate anticoagulation with replacement solution containing trisodium citrate will be associated with less bleeding complications compared to heparin with also a better filter survival Most important we want to evaluate the hypothesis that treatment with citrate will result in a lower mortality compared to treatment with systemic heparinization
Regional anticoagulation with trisodium citrate may also have some potential effects on the immune response as known from biocompatibility studies in intermittent hemodialysis Bioincompatibility leads to polymorphonuclear cell degranulation as indicated by the release of intracellular granule products such as myeloperoxidase lactoferrin lysozyme and elastase Citrate anticoagulation may lead to a lower polymorphonuclear cell degranulation since cations play a pivotal role in the process of cell activation and citrate creates an almost calcium-free environment within the dialyser by its virtue to chelate calcium
Primary endpoints
Mortality at day 28 after inclusion will be evaluated Survival time of the first hemofilter used will be determined including the cause of filter termination and the number of filters used in the first 72 hours the average filter patency time will be calculated
Citrate CVVH is stopped and thus also the study if the patient fulfils one of the following criteria
1 Total to ionised calcium ratio of more than 25
2 Persistent metabolic alkalosis with a BE of more than 10
3 Clinical signs of hypocalcaemia tetanic symptoms or prolonged QT interval
4 Progressive non-lactic acidosis pH 720 during CVVH combined with an increase in anion gap 13 without the presence of endo- or exogenous acids other than citrate suggesting citrate accumulation
Patients on heparin developing a HIT will continue CVVH with danaparoid anticoagulation Patients on heparin developing a bleeding episode will continue CVVH with regional citrate anticoagulation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None