Efficacy and Safety of Heparin-grafted Membrane for CRRT

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Acute Kidney Injury, Hemorrhage, Coagulopathy

Intervention / Treatment
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* Device: oXiris as first filter
* Device: M150 as first filter


Participation Criteria
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Eligibility Criteria
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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: Platelet count < 100 x 109 mm3 (but > 50) INR > 1.5 (but < 2.5) APTT > 50 seconds (but < 75) Post-surgery for < 48 hours Post-invasive procedures (eg. Pericardiocentasis) < 24 hrs Post major artery puncture or catheter removal from major arteries (carotids, subclavian, or femoral) < 24 hours 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

Ages Eligible for Study
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Minimum Age: 21 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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized initiation with oXiris versus M150 (conventional filter), with cross-over for subsequent circuits.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: oXiris as first filter<br>Start off the first CRRT circuit with oXiris, then cross-over to M150, then oXiris, then back to M150 | Device: oXiris as first filter<br>* 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<br>|
| Other: M150 as first filter<br>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<br>* start off with M150 as first hemofilter, then cross-over to oXiris when former clots, and then to M150, and then lastly to oXiris<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circuit lifespan, Continuous renal replacement therapy, Anticoagulation free, Bleeding risk, Acute kidney injury, Critical illness, Heparin-grafted membrane