Effect of Citrate on the Coagulation System in Patients Receiving CRRT

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to evaluate the effect of regional citrate anti-coagulation on different pathways of the coagulation system in critically ill patients with acute kidney injury. This will form the basis for future studies where the investigators plan to focus on patients with premature circuit clotting despite optimal post-filtrate ionised calcium parameters.

Detailed Description
-----------------
Purpose of clinical trial: To evaluate the effect of regional citrate anti-coagulation on different pathways of the coagulation system in critically ill patients with acute kidney injury. Patient population: critically ill patients with acute kidney injury requiring citrate-based continuous renal replacement therapy (CRRT) Primary objective: Changes from baseline in a number of measures of coagulability (platelet count; Prothrombin Time; Activated Partial Thromboplastin Time ratio; fibrinogen; d-dimers; Thrombin generation assay; Clot lysis; platelet function analysis 100) in both the blood within the patient's systemic circulation and the CRRT circuit over the course of 72 hours of regional anticoagulation with citrate. Number of Subjects/Patients: 12 patients with complete data. Trial Design: Prospective non-interventional study. Endpoints: Change from baseline in a number of measures of coagulability. Main Inclusion Criteria: Adult intensive care patients undergoing CRRT with citrate regional anti-coagulation for AKI.

Official Title
-----------------
The Effect of Regional Citrate Anti-coagulation on the Coagulation System in Critically Ill Patients Receiving Continuous Renal Replacement Therapy for Acute Kidney Injury - an Observational Cohort Study

Conditions
-----------------
Acute Kidney Failure

Intervention / Treatment
-----------------
* Procedure: CRRT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: acute kidney injury treated with citrate based continuous renal replacement therapy (CRRT) age >18 years. expected to require >72 hours of CRRT. Exclusion criteria: Known preexisting clotting tendency Known preexisting bleeding tendency Disseminated Intravascular Coagulation (DIC) Prior transfusion of any blood product in the 24 hours before enrolment Active bleeding (ie. needing blood transfusion) at time of enrolment Haemoglobin at time of enrolment <75g/L Haematocrit at time of enrolment >0.55 Patient would refuse Red Blood Cell transfusion (for example Jehova's Witness). Platelet count at time of enrolment <100x103/µL Treatment with any anticoagulant or antiplatelet agent at time of enrolment or within 7 days of enrolment with the exception of heparin or low molecular weight heparin for DVT prophylaxis. Intravenous heparin exposure within 4 hours of commencing citrate anticoagulation. Malnourished: BMI <18.5kg/m2 or unplanned weight loss >10% actual body weight (ABW) in preceding 6 months or BMI <20kg/m2 and unplanned weight loss >5% ABW in preceding 6 months. CRRT prescribed for an indication other than AKI (for example poisoning).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: CRRT|citrate based continuous renal replacement therapy|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of parameters of coagulability during Continuous Renal Replacement Therapy (CRRT) with citrate anticoagulation | Changes of coagulation parameters (Full Blood Count, prothrombin time, activated partial thromboplastin time ratio, fibrinogen, d-dimer, thrombin generation, clot lysis and platelet function analysis) during citrate-based CRRT | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of baseline coagulation status before initiation of citrate-based CRRT | Determination of parameters of coagulation [Full Blood Count (FBC), prothrombin time (PT), activated partial thromboplastin time ratio (APTTr), fibrinogen, D-dimers, antithrombin activity, protein C activity, free Protein S antigen, resistance to activated protein C screening, homocysteine, prothrombin 20210 mutation test, factor VIII level, Von Willebrand factor antigen, Dilute Russell's Viper Venom Time, dilute activated partial thromboplastin time, anticardiolipin antibodies, anti-beta 2 glycoprotein I antibodies, thrombin generation assay, clot lysis, platelet function 1+2, Thrombin-Antithrombin and platelet function analysis] before initiation of citrate-based CRRT | Before initiation of CRRT |