Citrate-based Regional Anticoagulation Versus Heparin for Continuous Renal Replacement Therapy

Study Overview
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Brief Summary
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Critically ill patients with acute kidney injury (AKI) are at high risk of bleeding on account of coagulopathy, platelet dysfunction, frequent liver dysfunction and invasive procedures.In patients at high risk of bleeding, anticoagulation restricted to the circuit (regional anticoagulation) has been advocated as the method of choice.However, citrate anticoagulation may have many metabolic consequences, such as metabolic alkalosis due to citrate metabolism into bicarbonate, and in patients with liver disease, metabolic acidosis and hypocalcemia may occur.Implementation of citrate-based regional anticoagulation with frequent monitoring of acid-base and electolytes is also more challenging for the nurses and does not eliminate the need of a low-dose systemic anticoagulation for thromboses prophylaxis in most of the patients. Citrate-based regional anticoagulation is therefore mainly advocated only for patients at high-risk of bleeding. The investigators plan to implement an open-label randomized control trial assessing the effectiveness of citrate-based regional anticoagulation in critically ill patients with AKI and with a special emphasis on the safety profile of this treatment in patients with severe liver failure.

Detailed Description
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monocentric prospective open-label randomized controlled trial at the ICU of the University Hospitals of Geneva (Switzerland). ICU patients eligible if they 18 yr old and had an AKI requiring CRRT Exclusion criteria Patients excluded if they had active hemorrhagic disorders or severe thrombocytopenia (< 50x109/L), a history of heparin-induced thrombocytopenia, severe liver failure defined as a factor V <20% or were on the waiting list for liver transplantation. Treatment assignment Subjects enrolled into the trial randomly allocated to either heparin or citrate anticoagulation

Official Title
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Citrate-based Regional Anticoagulation Versus Heparin for Continuous Renal Replacement Therapy in Critically Ill Patients With Acute Renal Failure: a Randomized Controlled Trial

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Device: citrate regional anticoagulation
* Device: citrate regional anticoagulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute kidney injury requiring renal replacement therapy (RIFLE criteria) Patients (males or females) > 18 yrs old Consent form signed (or in emergency investigator's statement form) Exclusion Criteria: Patients with active bleeding disorders Patients with past history of heparin-induced thrombocytopenia (HIT) Patients with very severe liver disease ( patients awaiting liver transplant or factor V < 20% or MELD score > 25) Pregnancy (negative pregnancy test required in child-bearing age women prior to inclusion) Enrollment in another concurrent therapeutic trial

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: heparin<br>CVVHDF performed using unfractionated heparin as anticoagulant and Prismasol as reinjection and dialysate fluids | Device: citrate regional anticoagulation<br>* Patients randomly allocated to 2 treatment groups: Treatment A: - Regional citrate-based anticoagulation with the Prismocitrate® 10/2 solution (GAMBRO) Treatment B: - Standard unfractionated heparin anticoagulation<br>Device: citrate regional anticoagulation<br>* Patients randomly allocated to 2 treatment groups: Treatment A: - Regional citrate-based anticoagulation with the Prismocitrate® 10/2 solution (GAMBRO) Treatment B: - Standard unfractionated heparin anticoagulation<br>|
| Active Comparator: citrate regional anticoagulation<br>CVVHDF performed using Prismocitrate 18/0 solution (Trisodium citrate 18 mmol/L | Device: citrate regional anticoagulation<br>* Patients randomly allocated to 2 treatment groups: Treatment A: - Regional citrate-based anticoagulation with the Prismocitrate® 10/2 solution (GAMBRO) Treatment B: - Standard unfractionated heparin anticoagulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean daily dialysis delivered dose during intensive care stay | Mean daily delivered dose during intensive care stay Filter life span | dialysis days during intensive care stay | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient survival |  | 28-day and 90-day patient survivals |