Regional Citrate Anticoagulation for RRT During V-V ECMO

Study Overview
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Brief Summary
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Anticoagulation is an essential component of all extracorporeal therapies. Currently locoregional citrate anticoagulation is the recommended technique for continuous renal replacement therapy (CRRT). However, low clearance of citrate restricts its use to blood flow up to 150 mL/min, preventing its use in ECMO. Renal replacement therapy (RRT) is commonly provided to ECMO patients with AKI. In presence of systemic heparinization for ECMO, additional anticoagulation for the CRRT circuit (i.e. RCA) is usually not employed. Nevertheless, thrombosis occurs more frequently in the CRRT circuit than the oxygenator because of the slower blood flow. The aim of this prospective, cross-over study is to assess, in patients undergoing CRRT during veno-venous ECMO (vv-ECMO), the efficacy and safety of adding regional citrate anticoagulation (RCA) for CRRT circuit anticoagulation.

Official Title
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Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy During Veno-venous ECMO: a Crossover Randomized Controlled Study

Conditions
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ARDS, Human, Acute Kidney Injury

Intervention / Treatment
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* Drug: Unfractionated heparin + RCA first
* Drug: Unfractionated heparin first


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted in ICU V-V ECMO support for acute respiratory failure CRRT therapy for acute kidney injury Exclusion Criteria: Pregnancy Pre-existing coagulation disorders Contraindication to heparin or citrate anticoagulation Moribund patients

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anticoagulation sequence 1 (UFH+ RCA)<br>UFH+ RCA first | Drug: Unfractionated heparin first<br>* Patients are randomized to receive this sequence of anticoagulation regimens: UFH / UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA<br>* Other names: Start with CVVHD, BF 200 ml/h, dialysate 2000 ml/h, systemic anticoagulation only;|
| Active Comparator: Anticoagulation sequence 2 (UFH)<br>UFH first | Drug: Unfractionated heparin + RCA first<br>* Patients are randomized to receive this sequence of anticoagulation regimens: UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA / UFH<br>* Other names: Start with CVVHD, BF 100-120 ml/min, dialysate 2000 ml/h, RCA + systemic anticoagulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of CRRT circuit clotting according to anticoagulation regimen | Rate of clotting in the intervention group (RCA+UFH) vs controls (UFH). I.e. : did the circuit clot in its 72h life? | According to the manufacturer recommendation elective RRT circuit replacement will be performed after 72 hours of circuit life. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRRT circuit survival analysis | Circuit life of RRT circuits in the intervention group (RCA+UFH) vs controls (UFH), comparison between groups will be performed as time to event(clotting) by log-rank test and described by the kaplan meier approach. Circuit replacement for other reasons (e.g. transfer to radiology to undergo a CT scan) will be right censored | According to the manufacturer recommendation elective RRT circuit replacement will be performed after 72 hours of circuit life. | 
| Comparison of platelets count, D-dimers, fibrinogen | Comparison of lab values of blood sampled during intervention (RCA+UFH) vs control (UFH). Values will be compared as absolute value and as a difference compared to each circuit baseline | 72 hours for each circuit | 
| Incidence of citrate anticoagulation side-effects | Total to ionized calcium ratio (marker of citrate accumulation), rate of hypersodiemia and alkalosis will be compared between intervention (RCA+UFH) and control (UFH) | 72 hours for each circuit | 
| To evaluate the anticoagulation effects of UFH and RCA | TEG analysis of blood samples with UFH vs UFH+RCA effect will be compared. Specifically, TEG R-time will be compared in blood sampled from circuit anti-coagulated with RCA+UFH vs UFH only | 72 hours for each circuit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, Extracorporeal Membrane Oxygenation, Acute Kidney Injury, Renal Replacement Therapy