Efficacy and Safety of Heparin-grafted Membrane for CRRT (CARROM)

Continuous Renal Replacement Therapy With Anticoagulation-free Regimen in Bleeding-risk Patients Using oXiris Membrane - CARROM Study

The investigators hypothesize that the use of heparin-grafted membrane versus conventional membrane in critically-ill patients with bleeding-risk undergoing continuous renal replacement therapy, will effectively prolong the circuit lifespan, without worsening of the systemic APTT or underlying bleeding risk.

Study Overview

• Status: Completed
• Conditions: Hemorrhage; Acute Kidney Injury; Coagulopathy
• Intervention / Treatment: Device: oXiris as first filter; Device: M150 as first filter

Detailed Description

Aims and objectives:

We aim to compare the performance and safety of heparin-grafted AN69 membrane (oXiris, Gambro) with the conventional AN69 membrane (M150, Gambro) without systemic anticoagulation during continuous renal replacement therapy (CRRT), in critically ill patients with acute kidney injury (AKI) admitted to the intensive care unit (ICU), who has moderate bleeding risk and in whom systemic anticoagulation is contraindicated.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 119228
    • National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Adult patients (age 21 and above) who are admitted to ICUs or CCU and requiring CRRT for acute kidney injury or ESRD Patients who has moderate bleeding risk (see below definitions) Patients with NO systemic or regional circuit anticoagulation Informed consent taken from the patient, or proxy if the former is unable to sign due to medical reasons Anticipated need for prolonged CRRT > 3 days

(Moderate bleeding risk criteria:)

Moderate bleeding risk is defined by any of the following:

1. Platelet count < 100 x 109 mm3 (but > 50)
2. INR > 1.5 (but < 2.5)
3. APTT > 50 seconds (but < 75)
4. Post-surgery for < 48 hours
5. Post-invasive procedures (eg. Pericardiocentasis) < 24 hrs
6. Post major artery puncture or catheter removal from major arteries (carotids, subclavian, or femoral) < 24 hours
7. Recent internal or gastrointestinal bleeding within 48 hours (should be secured bleeding with no relapse noted)

Exclusion Criteria:

Patients with very high bleeding risk (for which they should also fall outside of the below inclusion criteria - see below) Patients who are known to have heparin-induced thrombocytopenia or allergic to heparin Patients with other medical conditions for which heparin is contraindicated. Patients who require systemic anticoagulation for medical indications (We will accept patients who are on prophylactic doses of anticoagulation for DVT prophylaxis) Patients who are pregnant Patients/legally accepted surrogate who decline to consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: oXiris as first filter; Start off the first CRRT circuit with oXiris, then cross-over to M150, then oXiris, then back to M150	Device: oXiris as first filter; 2 arms - each start off CRRT with either oXiris or M150 as first hemofilter, and then do cross-over to either hemofilters in a sequential manner when the former clots
Other: M150 as first filter; Patients in M150 arm will start off with M150 as first filter for CRRT, then cross-over to oXiris after the former clots, then back to M150, then to oXiris.	Device: M150 as first filter; start off with M150 as first hemofilter, then cross-over to oXiris when former clots, and then to M150, and then lastly to oXiris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circuit lifespan during continuous renal replacement therapy (up till termination as defined above) with each dialyzer (oXiris or M150)	Circuit lifespan	usually 10 - 30 hours from commencement of circuit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-circuit INR/APTT, and post-circuit INR/APTT 2 hours after termination. (We will be using the 2 hour post-circuit APTT result of the preceding dialyzer, as the pre-circuit APTT for the subsequent dialyzer.	effect on coagulation status	Usually after 10-30 hours when dialyzer clots
Serum urea/creatinine, and effluent urea/creatinine (paired samples) at 4 hrs from each circuit commencement, to examine "protein layering" and solute clearance.	effect on clearance	Usually 4 hours into circuit commencement
Transmembrane pressure (TMP), pressure drop across hemodiafilter (PDF), pressure in (PI), will be recorded on hourly basis throughout treatment, as per usual nursing protocol.	effect on circuit pressures	over 10-30 hours of circuit running

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total inotropic score, which is defined as total quantities of Dopamine + Dobutamine + 100 (Noradrenaline) + 100 (Adrenaline) in mcg/kg/min; pre- and post- use of the circuit.	effect on hemodynamics	usually after 10-30 hours of circuit lifespan
Urine output over the 6 hours preceding the commencement of first circuit, and 6 hours after termination of the first circuit.	effect on oliguria	Usually after 10-30 hours of circuit lifespan

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Investigators: Principal Investigator: Horng-Ruey Chua, MBBS, National University Health System

Publications and helpful links

General Publications

• Tsujimoto Y, Miki S, Shimada H, Tsujimoto H, Yasuda H, Kataoka Y, Fujii T. Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2021 Sep 14;9(9):CD013330. doi: 10.1002/14651858.CD013330.pub2.
• Schetz M, Van Cromphaut S, Dubois J, Van den Berghe G. Does the surface-treated AN69 membrane prolong filter survival in CRRT without anticoagulation? Intensive Care Med. 2012 Nov;38(11):1818-25. doi: 10.1007/s00134-012-2633-x. Epub 2012 Jul 7.
• Uchino S, Fealy N, Baldwin I, Morimatsu H, Bellomo R. Continuous is not continuous: the incidence and impact of circuit "down-time" on uraemic control during continuous veno-venous haemofiltration. Intensive Care Med. 2003 Apr;29(4):575-8. doi: 10.1007/s00134-003-1672-8. Epub 2003 Feb 8.
• Evenepoel P, Dejagere T, Verhamme P, Claes K, Kuypers D, Bammens B, Vanrenterghem Y. Heparin-coated polyacrylonitrile membrane versus regional citrate anticoagulation: a prospective randomized study of 2 anticoagulation strategies in patients at risk of bleeding. Am J Kidney Dis. 2007 May;49(5):642-9. doi: 10.1053/j.ajkd.2007.02.001.
• Tan HK, Baldwin I, Bellomo R. Continuous veno-venous hemofiltration without anticoagulation in high-risk patients. Intensive Care Med. 2000 Nov;26(11):1652-7. doi: 10.1007/s001340000691.
• Chua HR, Baldwin I, Bailey M, Subramaniam A, Bellomo R. Circuit lifespan during continuous renal replacement therapy for combined liver and kidney failure. J Crit Care. 2012 Dec;27(6):744.e7-15. doi: 10.1016/j.jcrc.2012.08.016. Epub 2012 Oct 24.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: January 27, 2013
• First Submitted That Met QC Criteria: January 29, 2013
• First Posted (Estimate): January 30, 2013

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 25, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Critical illness; Acute kidney injury; Bleeding risk; Continuous renal replacement therapy; Heparin-grafted membrane; Circuit lifespan; Anticoagulation free
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Hemorrhage; Acute Kidney Injury
• Other Study ID Numbers: DSRB 2012/02222; NKFRC/2012/01/11 (Other Grant/Funding Number: National Kidney Foundation Singapore)

Plan for Individual participant data (IPD)

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