Regional Citrate Anticoagulation for RRT During V-V ECMO

Acute Kidney Injury Clinical Trial

— CRRT ECMO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05148026
• Other study ID #: 3732
• Status: Recruiting
• Phase: N/A
• Start date: November 14, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2023
• Source: University of Milano Bicocca
• Contact: Marco Giani
• Phone: +390392333666
• Email: marco.giani[@]unimib.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• ARDS, Human
• Respiratory Distress Syndrome

Intervention

Drug:
• Unfractionated heparin + RCA first
Patients are randomized to receive this sequence of anticoagulation regimens: UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA / UFH
• Unfractionated heparin first
Patients are randomized to receive this sequence of anticoagulation regimens: UFH / UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA

Locations

Country	Name	City	State
Italy	ASST MONZA-Rianimazione Generale	Monza

Sponsors (1)

Lead Sponsor	Collaborator
University of Milano Bicocca

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Giani M, Scaravilli V, Stefanini F, Valsecchi G, Rona R, Grasselli G, Bellani G, Pesenti AM, Foti G. Continuous Renal Replacement Therapy in Venovenous Extracorporeal Membrane Oxygenation: A Retrospective Study on Regional Citrate Anticoagulation. ASAIO J — View Citation

Schilder L, Nurmohamed SA, Bosch FH, Purmer IM, den Boer SS, Kleppe CG, Vervloet MG, Beishuizen A, Girbes AR, Ter Wee PM, Groeneveld AB; CASH study group. Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in cr — View Citation

Shum HP, Kwan AM, Chan KC, Yan WW. The use of regional citrate anticoagulation continuous venovenous hemofiltration in extracorporeal membrane oxygenation. ASAIO J. 2014 Jul-Aug;60(4):413-8. doi: 10.1097/MAT.0000000000000085. — View Citation

Stucker F, Ponte B, Tataw J, Martin PY, Wozniak H, Pugin J, Saudan P. Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled tri — View Citation

Zarbock A, Kullmar M, Kindgen-Milles D, Wempe C, Gerss J, Brandenburger T, Dimski T, Tyczynski B, Jahn M, Mulling N, Mehrlander M, Rosenberger P, Marx G, Simon TP, Jaschinski U, Deetjen P, Putensen C, Schewe JC, Kluge S, Jarczak D, Slowinski T, Bodenstein — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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
Secondary	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
Secondary	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