Citrate Anticoagulation During MARS Treatment

Study Overview
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Brief Summary
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The optimal anticoagulation procedure during MARS treatment has not been defined. In various multi-centre trials, such as MARS-RELIEF, anticoagulation procedures are left to the discretion of the treating physician. On the one hand, given the increased risk of bleeding associated with liver failure, high dosage of anticoagulation therapy should be avoided. On the other hand, contact of blood or blood components with the extracorporeal circuit will likely result in coagulation activation or even loss of coagulation factors. Citrate anticoagulation has gained popularity, especially in hemodialysis patients. It results in a highly effective anticoagulation, exclusively confined to the extracorporeal circulation. Moreover, dependent on the type of dialyser membrane, citrate anticoagulation resulted in reduced activation of other cellular components. In contrast to hemodialysis patients, experience with citrate anticoagulation during treatment with artificial liver devices is limited. The liver contributes substantially to the metabolism of exogenous citrate. As a result, cirrhotic patients have decreased endogenous citrate clearances. Importantly, blood purification devices contribute substantially to overall citrate clearance, thereby preventing accumulation of citrate. Several centres, including our own, have gained experience with citrate anticoagulation during fractionated plasma separation and adsorption (FPSA), a related liver dialysis device, in the treatment of liver failure patients. Citrate anticoagulation during MARS treatment has not been studied so far.

Official Title
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Citrate Anticoagulation During MARS Treatment

Conditions
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Liver Failure

Intervention / Treatment
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* Drug: trisodiumcitrate
* Drug: trisodiumcitrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled MARS treatment Age over 18 years Informed consent Admitted to Intensive Care Unit Exclusion Criteria: Blood or plasma transfusion within 48 hours before study Hypocalcemia (ionised Ca < 0.90 mmol/l) Acidosis (pH < 7.25) due to any cause Use of citrate containing medications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>citrate first | Drug: trisodiumcitrate<br>* trisodiumcitrate 1.035 M<br>|
| Experimental: B<br>no anticoagulation first | Drug: trisodiumcitrate<br>* trisodiumcitrate 1.035 M<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extracorporeal circuit coagulation events |  | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Citrate tolerability |  | 6 hours | 
| Treatment efficacy |  | 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MARS treatment, Citrate anticoagulation