Investigating Different Anticoagulants for Renal Replacement Therapy

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effect of regional citrate anticoagulation within the scope of continuous renal replacement (CRRT) in critically ill patients with acute kidney injury (AKI) on filter life span and 90-day all cause mortality.

Detailed Description
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Purpose of clinical trial: To evaluate the effect of regional citrate anticoagulation within the scope of continuous renal replacement (CRRT) in critically ill patients with acute kidney injury (AKI) on filter life span and 90-day all cause mortality. Patient population: critically ill patients with acute kidney injury requiring renal replacement therapy. Primary objective: Anticoagulation of the extracorporeal circuit is required in continuous RRT (CRRT). To this date, it is not clear which anticoagulant should be used for CRRT. Regional citrate anticoagulation (RCA) for CRRT in critically ill patients with AKI prolongs filter life span and reduces 90-day all cause mortality by approximately 8% (from 48% to 40%) compared to systemic heparin anticoagulation for CRRT

Official Title
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Regional Citrate Versus Systemic Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Drug: Heparin
* Drug: Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Critically ill patients with clinical indication for CRRT (clinical decision to use continuous RRT due to hemodynamic instability) Or Severe acute kidney injury (KDIGO 3-classification) despite optimal resuscitation At least one of the following conditions Sepsis or septic shock Use of catecholamines (norepinephrine or epinephrine ≥ 0.1 µg/kg/min or norepinephrine ≥ 0.05 µg/kg/min + dobutamine (any dose) or norepinephrine ≥ 0.05 µg/kg/min + vasopressin (any dose) or epinephrine ≥ 0.05 µg/kg/min + norepinephrine ≥ 0.05 µg/kg/min) Refractory fluid overload: worsening pulmonary edema: PaO2/FiO2 < 300 mmHg and/or fluid balance > 10% of body weight) 18-90 years old Intention to provide full intensive care treatment for at least 3 days Written informed consent of the patient or the legal representatives or the authorized representative or the inclusion due to an emergency situation Exclusion Criteria: Patients with increased bleeding risk (e.g. an active bleeding from ulcers in the gastro-intestinal tract, hypertension with a diastolic blood pressure higher than 105 mm Hg, injuries (intracranial hemorrhage, aneurysm of brain arteries) of or surgical procedures on the central nervous system if a heparinization with a target aPTT 45-60 s is not allowed by the treating neurologist or neurosurgeon, severe retinopathies, bleeding into the vitreum, ophthalmic surgical procedures)) or injuries, active tuberculosis; infective endocarditis) Disease or organ damage related with hemorrhagic diathesis (coagulopathy, thrombocytopenia, severe liver or pancreas disease) Dialysis-dependent chronic kidney insufficiency Need of therapeutic systemic anticoagulation Allergic reaction to one of the anticoagulants or ingredients, Heparin-induced thrombocytopenia AKI caused by permanent occlusion or surgical lesion of the renal artery AKI caused by (glomerulo)nephritis, interstitial nephritis, vasculitis or postrenal obstruction Do-not-resuscitate order Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura Persistent and severe lactate acidosis in the context of an acute liver failure and/or shock Kidney transplant within the last 12 months Pregnancy and nursing period Abortus imminens No hemofiltration machine free for use at the moment of inclusion Participation in another clinical intervention trial in the last 3 months Persons with any kind of dependency on the investigator or employed by the sponsor or investigator Persons held in an institution by legal or official order

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: heparin anticoagulation<br>Systemic anticoagulation of the continuous renal replacement therapy with heparin. Dose will be titrated to maintain aPTT (activated partial thromboplastin time) between 45-60s) | Drug: Heparin<br> <br> |
| Experimental: citrate anticoagulation<br>Regional anticoagulation of the continuous renal replacement therapy with citrate. Target posthemofilter ionized calcium level: 0.25-0.35 mmol/l | Drug: Citrate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRRT-filter life span in hours | It will be reported how long the filter will be used during CRRT | during continuous renal replacement therapy up to 1 year | 
| Overall survival in a 90day follow-up period |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU length of stay in days | The primary ICU stay will be documented. | up to 1 year | 
| Hospital length of stay in days |  | up to 1 year | 
| duration of renal replacement therapy | within 1 year after randomization | 1 year | 
| Bleeding complication |  | intraoperative | 
| Number of patients with administration of red blood cells |  | intraoperative | 
| Rate of infection |  | during primary ICU stay up to 1 year | 
| Major adverse kidney events |  | day 28, 60, 90 and after 1 year after start of CRRT | 
| Complications of therapy |  | intraoperative | 
| Recovery of renal function | The recovery of renal function will be defined as composite endpoint consisting of lack of dialysis dependency and serum creatinine level no more than 0.5 mg/dl above the baseline value) | day 28, 60, 90 and 1 year after start of CRRT | 
| Number of participants with hemodialysis |  | day 28, 60, 90 and 1 year after start of CRRT | 
| Mortality |  | day 28, 60 and 1-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRRT, AKI, anticoagulation, KDIGO