Multi-center Study to Investigate the Effects of Citrasate® on Heparin N Requirements During Hemodialysis Treatment

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the use of Citrasate®, citric acid dialysate enables the reduction of the heparin N (anticoagulant) dose in patients undergoing hemodialysis.

Detailed Description
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During hemodialysis, waste products are removed from the blood by diffusion across the dialyzer membrane into an electrolyte solution known as dialysate. Dialysate is produced from acid concentrate, bicarbonate solution and water using a three stream proportioning system that mixes the acid concentrate, bicarbonate and water to produce the final dialysate. Patients are typically anticoagulated with heparin during dialysis to prevent blood from clotting in the extracorpoeial circuit. Heparin use is associated with significant risks including the possibility of bleeding, heparin induced thrombocytopenia (HIT) and contamination. For these reasons, the possibility of reducing heparin dose while maintaining HD adequacy is clinically attractive. Citrasate® is an FDA approved acid concentrate that contains citric acid (citrate) rather than acetic acid (acetate) which is traditionally used in acid concentrate. Citrate in higher concentrations is also a known anticoagulant. We are therefore conducting this study to determine whether the use of Citrasate, citric acid dialysate enables the reduction of the heparin requirements in patients undergoing hemodialysis.

Official Title
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Citrasate® Effect On Heparin N Requirements During Hemodialysis Treatment: A Phase IV,Study to Investigate the Effects of Citrasate on Heparin N Requirements During Hemodialysis Treatment in Subjects Maintained on Thrice Weekly Hemodialysis

Conditions
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Renal Dialysis

Intervention / Treatment
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* Drug: Heparin N reduction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is capable of giving informed consent, or has an acceptable surrogate capable of giving consent on the subject's behalf. ESRD maintained on thrice weekly HD Stable Heparin prescription (Heparin dose) for the previous 4 weeks Dialyzed using bolus heparin anticoagulation with dose >/= 2000 units per treatment Hgb >/= 9.5 prior to study start eKt/V >/= 1.0 (or spKt/V >/= 1.2) in the monthly lab work prior to study start Exclusion Criteria: Any laboratory abnormality, medical condition or psychiatric disorder which in the opinion of the investigator would put the subject's disease management at risk or may result in the subject being unable to comply with study requirements Patient is maintained on Coumadin therapy or LMW heparin Known history of HIT, coagulopathy or any other bleeding and/or thrombotic disorders Patients dialyzed with < 2000 units of Heparin per treatment Dialyzed without heparin Known pregnancy Dialyzed with reuse of hemodialyzers Documented clotted dialyzer or dialysis lines in last 30 days (1 month) requiring changing dialyzer, bloodlines or terminating treatment Randomized in a clinical trial involving anticoagulation in the last 30 days

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Citrasate and heparin reduction<br>Sequential hemodialysis treatment study in which all enrollees move through four (4) separate treatment phases. Results from the separate phases will be compared to standard bicarbonate dialysis with standard does of heparin. | Drug: Heparin N reduction<br>* Dialysis with Citrasate, acid concentrate plus 100% of patient's standard heparin N dose; Dialysis with Citrasate acid concentrate plus 80% of patient's standard heparin N dose; Dialysis with Citrasate acid concentrate plus 66.7% of patient's standard heparin N dose.<br>* Other names: Heparin N;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of dialyzer conductivity clearance (KECN) when dialyzed with Citrasate, acid concentrate and 80% of baseline Heparin dose compared to dialysis using standard bicarbonate dialysate and standard dose heparin N (baseline). |  | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of conductivity clearance when dialyzed with Citrasate and 66.7% baseline Heparin dose as compared to baseline. |  | Baseline and 6 months | 
| Dialyzer or system clotting with Citrasate plus reduced Heparin compared to baseline. |  | baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End Stage Renal Disease, Renal Dialysis, Hemodialysis therapy, Heparin, Citrasate, Anticoagulant