Regional Citrate Anticoagulation for RRT During V-V ECMO

NCT05148026 | Completed

• 1 other identifier: 3732
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

ARDS, Human; Acute Kidney Injury

Keywords

Extracorporeal Membrane Oxygenation; Acute Kidney Injury; ARDS; Renal Replacement Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• CRRT circuit "survival" analysis

  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

  72 hours for each circuit

• Incidence of citrate anticoagulation side-effects

  72 hours for each circuit

• To evaluate the anticoagulation effects of UFH and RCA

  72 hours for each circuit

Study Arms (2)

Anticoagulation sequence 1 (UFH+ RCA)

ACTIVE COMPARATOR

UFH+ RCA first

Drug: Unfractionated heparin first

Anticoagulation sequence 2 (UFH)

ACTIVE COMPARATOR

UFH first

Drug: Unfractionated heparin + RCA first

Interventions

Unfractionated heparin + RCA first DRUG

Patients are randomized to receive this sequence of anticoagulation regimens: UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA / UFH

Also known as: Start with CVVHD, BF 100-120 ml/min, dialysate 2000 ml/h, RCA + systemic anticoagulation

Anticoagulation sequence 2 (UFH)

Unfractionated heparin first DRUG

Patients are randomized to receive this sequence of anticoagulation regimens: UFH / UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA

Also known as: Start with CVVHD, BF 200 ml/h, dialysate 2000 ml/h, systemic anticoagulation only

Anticoagulation sequence 1 (UFH+ RCA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted in ICU
• V-V ECMO support for acute respiratory failure
• CRRT therapy for acute kidney injury

You may not qualify if:

• Pregnancy
• Pre-existing coagulation disorders
• Contraindication to heparin or citrate anticoagulation
• Moribund patients

Sponsors & Collaborators

• University of Milano Bicocca: lead

Study Sites (1)

ASST MONZA-Rianimazione Generale

Monza, Italy, 20900, Italy

Location

Related Publications (6)

• 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 M, Meybohm P, Wirtz S, Moerer O, Kortgen A, Simon P, Bagshaw SM, Kellum JA, Meersch M; RICH Investigators and the Sepnet Trial Group. Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury: A Randomized Clinical Trial. JAMA. 2020 Oct 27;324(16):1629-1639. doi: 10.1001/jama.2020.18618.

  PMID: 33095849 RESULT

• 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. 2020 Mar;66(3):332-338. doi: 10.1097/MAT.0000000000001003.

  PMID: 31045918 RESULT

• 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.

  PMID: 24727536 RESULT

• 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 critically ill patients with acute kidney injury: a multi-center randomized clinical trial. Crit Care. 2014 Aug 16;18(4):472. doi: 10.1186/s13054-014-0472-6.

  PMID: 25128022 RESULT

• 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 trial. Crit Care. 2015 Mar 18;19(1):91. doi: 10.1186/s13054-015-0822-z.

  PMID: 25881975 RESULT

• Giani M, Frazzei M, Rona R, Langer T, Pozzi M, Foti G, Rezoagli E; CRRT ECMO Study Group. Regional citrate anticoagulation for renal replacement therapy during venovenous ECMO: A randomized crossover pilot study. Ann Intensive Care. 2026 Apr 27;16:100072. doi: 10.1016/j.aicoj.2026.100072. eCollection 2026.

  PMID: 42088147 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Acute Kidney Injury

Interventions

Heparin; Continuous Renal Replacement Therapy; Dialysis Solutions

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Renal Replacement Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Collaborator

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: December 8, 2021
• Study Start: November 14, 2021
• Primary Completion: July 30, 2025
• Study Completion: July 31, 2025
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)