Effect of Citrate on the Coagulation System in Patients Receiving CRRT (Citroco)

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Failure
• Intervention / Treatment: Procedure: CRRT

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.

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Guy's & St Thomas Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

adults with acute kidney injury requiring citrate based continuous renal replacement therapy

Description

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).

Study Plan

How is the study designed?

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

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Investigators: Principal Investigator: Marlies Ostermann, PhD, Guy's & St Thomas' Foundation Hospital

Publications and helpful links

General Publications

• Fisher R, Moore GW, Mitchell MJ, Dai L, Crichton S, Lumlertgul N, Ostermann M. Effects of regional citrate anticoagulation on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving continuous renal replacement therapy for acute kidney injury: a prospective study. Ann Intensive Care. 2022 Mar 31;12(1):29. doi: 10.1186/s13613-022-01004-w.
• Fisher R, Lei K, Mitchell MJ, Moore GW, Dickie H, Tovey L, Crichton S, Ostermann M. 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. BMC Nephrol. 2017 Oct 2;18(1):304. doi: 10.1186/s12882-017-0718-z.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: June 26, 2015
• First Posted (Estimate): July 1, 2015

Study Record Updates

• Last Update Posted (Actual): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 21, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: RJ114/N168

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO