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Regional Citrate Anticoagulation for RRT During V-V ECMO (CRRT ECMO)

Primary Purpose

ARDS, Human, Acute Kidney Injury

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Unfractionated heparin + RCA first
Unfractionated heparin first
Sponsored by
University of Milano Bicocca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ARDS, Human focused on measuring Extracorporeal Membrane Oxygenation, Acute Kidney Injury, ARDS, Renal Replacement Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • ASST MONZA-Rianimazione GeneraleRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Anticoagulation sequence 1 (UFH+ RCA)

Anticoagulation sequence 2 (UFH)

Arm Description

UFH+ RCA first

UFH first

Outcomes

Primary Outcome Measures

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?

Secondary Outcome Measures

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
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
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)
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

Full Information

First Posted
October 26, 2021
Last Updated
January 24, 2023
Sponsor
University of Milano Bicocca
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1. Study Identification

Unique Protocol Identification Number
NCT05148026
Brief Title
Regional Citrate Anticoagulation for RRT During V-V ECMO
Acronym
CRRT ECMO
Official Title
Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy During Veno-venous ECMO: a Crossover Randomized Controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 14, 2021 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Milano Bicocca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ARDS, Human, Acute Kidney Injury
Keywords
Extracorporeal Membrane Oxygenation, Acute Kidney Injury, ARDS, Renal Replacement Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Anticoagulation sequence 1 (UFH+ RCA)
Arm Type
Active Comparator
Arm Description
UFH+ RCA first
Arm Title
Anticoagulation sequence 2 (UFH)
Arm Type
Active Comparator
Arm Description
UFH first
Intervention Type
Drug
Intervention Name(s)
Unfractionated heparin + RCA first
Other Intervention Name(s)
Start with CVVHD, BF 100-120 ml/min, dialysate 2000 ml/h, RCA + systemic anticoagulation
Intervention Description
Patients are randomized to receive this sequence of anticoagulation regimens: UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA / UFH
Intervention Type
Drug
Intervention Name(s)
Unfractionated heparin first
Other Intervention Name(s)
Start with CVVHD, BF 200 ml/h, dialysate 2000 ml/h, systemic anticoagulation only
Intervention Description
Patients are randomized to receive this sequence of anticoagulation regimens: UFH / UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA
Primary Outcome Measure Information:
Title
Incidence of CRRT circuit clotting according to anticoagulation regimen
Description
Rate of clotting in the intervention group (RCA+UFH) vs controls (UFH). I.e. : did the circuit clot in its 72h life?
Time Frame
According to the manufacturer recommendation elective RRT circuit replacement will be performed after 72 hours of circuit life.
Secondary Outcome Measure Information:
Title
CRRT circuit "survival" analysis
Description
"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
Time Frame
According to the manufacturer recommendation elective RRT circuit replacement will be performed after 72 hours of circuit life.
Title
Comparison of platelets count, D-dimers, fibrinogen
Description
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
Time Frame
72 hours for each circuit
Title
Incidence of citrate anticoagulation side-effects
Description
Total to ionized calcium ratio (marker of citrate accumulation), rate of hypersodiemia and alkalosis will be compared between intervention (RCA+UFH) and control (UFH)
Time Frame
72 hours for each circuit
Title
To evaluate the anticoagulation effects of UFH and RCA
Description
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
Time Frame
72 hours for each circuit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marco Giani
Phone
+390392333666
Email
marco.giani@unimib.it
Facility Information:
Facility Name
ASST MONZA-Rianimazione Generale
City
Monza
ZIP/Postal Code
20900
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marco Giani
Phone
+39 0392333666
Email
marco.giani@unimib.it

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33095849
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 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.
Results Reference
result
PubMed Identifier
31045918
Citation
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.
Results Reference
result
PubMed Identifier
24727536
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.
Results Reference
result
PubMed Identifier
25128022
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 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.
Results Reference
result
PubMed Identifier
25881975
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 trial. Crit Care. 2015 Mar 18;19(1):91. doi: 10.1186/s13054-015-0822-z.
Results Reference
result

Learn more about this trial

Regional Citrate Anticoagulation for RRT During V-V ECMO

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