Comparison of Slow Efficiency Daily Dialysis (SLEDD) With Unfractionated Heparin Versus Citrasate in Critically Ill Patients.

Study Overview
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Brief Summary
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The purpose of this study is to compare the feasibility, safety and efficacy of hemodialysis with unfractionated heparin compared to hemodialysis with Citrasate in Critically Ill Patients.

Detailed Description
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Objective : To compare the feasibility, safety and efficacy of Sustained Low Efficiency Daily Hemodialysis (SLEDD) using regional anticoagulation with Citrasate® compared to systemic anticoagulation with unfractionated heparin in critically ill patients. Design : Prospective, randomized, single-center clinical trial Setting : mixed medical-surgical 45 bed ICU in a tertiary university hospital Patients : 250 patients with Acute Kidney Injury (AKI) stage III needing renal replacement therapy Interventions : Patients are randomized to receive SLEDD using standard dialysate and systemic anticoagulation with UF versus SLEDD using Citrasate®-dialysate with no additional UF. Measurements and main results : Primary end point : - The incidence of premature interruptions of the dialysis procedure attributed to hemofilter clotting. Secondary end points : The incidence of bleeding episodes as defined by the WHO-criteria The transfusion requirements The incidence of technique failure The incidence of metabolic derangements (metabolic alkalosis, metabolic acidosis, hypocalcemia, hypercalcemia, hypernatremia, hyponatremia) The incidence of citrate intoxication The dialysis efficiency expressed as Kt/V and URR Tertiary end points : - All cause mortality at day 28 and day 90 after inclusion

Official Title
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Comparison of Slow Efficiency Daily Dialysis (SLEDD) With Unfractionated Heparin Versus Citrasate in Critically Ill Patients.

Conditions
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Acute Kidney Injury, Hemodialysis

Intervention / Treatment
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* Drug: Unfractionated heparin
* Drug: Citrasate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Need for hemodialysis in the ICU for at least one treatment No prior hemodialysis treatment in the ICU except continuous renal replacement therapy Exclusion Criteria: Need for systemic anticoagulation with unfractionated or fractionated heparin, oral anticoagulants or intravenous anti-aggregants for other reasons Need for continued thrombolysis therapy within the 6 hours before inclusion Need for continued treatment with activated protein C (drotrecogin alfa) within the 12 hours before inclusion Need for continued treatment with intravenous anti-aggregants (abciximab, eptifabide) within 12 hours before inclusion Liver failure (acute and acute-on-chronic) Confirmed or suspected Heparin Induced Thrombocytopenia (HIT) Heparin allergies Severe uncorrected hypocalcemia (ionized calcium < 0,8 mmol/l) Refusal of informed consent

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Anticoagulation<br>Hemodialysis is performed using standard anticoagulation using unfractionated heparin if no contra-indications for the use of heparin exist. If contra-indications for heparin exist a heparin coated hemofilter (Evodial) will be used. The use of unfractionated heparin or no heparin (with coated hemofilter) is a decision to be taken before every hemodialysis. | Drug: Unfractionated heparin<br>* dose 5-10 IU/kg/hrs adaptations of infusion rate upon APTT measurements during hemodialysis<br>* Other names: Unfractionated Heparin, LEO laboratories Ltd, MA #PL 0043/0041R;|
| Experimental: Citrasate<br>Hemodialysis is performed with Citrasate | Drug: Citrasate<br>* Citrasate is infused as a dialysate<br>* Other names: Citrasate, Advanced Renal Technologies, MA #K000792;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of premature interruptions of the dialysis procedure attributed to hemofilter clotting. |  | 6 hours after starting dialysis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of technique failure defined as the number of patients who develop a contra-indication for the allocated anticoagulation regimen during the study period |  | during whole wtudy | 
| The incidence of bleeding episodes. A bleeding episode is defined according to the WHO bleeding criteria |  | during the whole study period | 
| The transfusion requirements defined as the total of units blood products administrated during the ICU stay and per dialysis treatment |  | during the whole study period | 
| The incidence of metabolic derangements during the study period | Metabolic alkalosis (defined as a pH > 7,5 and a bicarbonate > 24 mmol/l) Metabolic acidosis (defined as a pH < 7,25 and a bicarbonate < 18 mmol/l) Hypocalcemia (defined as an ionized calcium < 0,9 mmol/l) Hypercalcemia (defined as an ionized calcium > 1,2 mol/l) Hypernatremia (defined as a Na+ > 145 mmol/l) Hyponatremia (defined a a Na+ < 130 mmol/l) Citrate toxicity (defined as a total calcium/ionized calcium ratio > 2,5) | during the whole study period | 
| Dialysis efficiency expressed as Kt/V and URR |  | 6 hours after starting dialysis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anticoagulation, Intensive Care Medicine, Hemodialysis, Critical Ill Patients