ARDS, HumanCRRT ECMONCT05148026
Regional Citrate Anticoagulation for RRT During V-V ECMO
A study testing Unfractionated heparin + RCA first and Unfractionated heparin first in people with ARDS, Human and Acute Kidney Injury, run by University of Milano Bicocca at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ARDS, Human, Acute Kidney Injury
- What is being tested?
- Unfractionated heparin + RCA first and Unfractionated heparin first
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteItaly
- Study dates
- 14 Nov 2021to 31 Jul 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients admitted in ICU
- V-V ECMO support for acute respiratory failure
- CRRT therapy for acute kidney injury
Who cannot join
- Pregnancy
- Pre-existing coagulation disorders
- Contraindication to heparin or citrate anticoagulation
- Moribund patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy During Veno-venous ECMO: a Crossover Randomized Controlled Study
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.
Read more
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
- Being tested
- Unfractionated heparin + RCA first, Unfractionated heparin first
- Keywords
- Extracorporeal Membrane Oxygenation, Acute Kidney Injury, ARDS, Renal Replacement Therapy
- Medical subject headings
- Respiratory Distress Syndrome, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Unfractionated heparin + RCA firstDrug
Also called Start with CVVHD, BF 100-120 ml/min, dialysate 2000 ml/h, RCA + systemic anticoagulation
Patients are randomized to receive this sequence of anticoagulation regimens: UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA / UFH
Unfractionated heparin firstDrug
Also called Start with CVVHD, BF 200 ml/h, dialysate 2000 ml/h, systemic anticoagulation only
Patients are randomized to receive this sequence of anticoagulation regimens: UFH / UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA
| Study group | Role | What they receive |
|---|---|---|
| Anticoagulation sequence 1 (UFH+ RCA) | Active comparator | UFH+ RCA first Receives: Drug: Unfractionated heparin first |
| Anticoagulation sequence 2 (UFH) | Active comparator | UFH first Receives: Drug: Unfractionated heparin + RCA first |
What is being measured
The primary outcome is the main question the study is designed to answer.
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?
Measured: 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
"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
Measured: 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
Measured: 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)
Measured: 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
Measured: 72 hours for each circuit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2021
- Study start14 Nov 2021
- Primary completion30 Jul 2025
- Study completion31 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for ARDS, HumanStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milano Bicocca
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marco Giani, University of Milano Bicocca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05148026
- Sponsor's protocol ID
- 3732
- Acronym
- CRRT ECMO
- Status last verified
- May 2026
- First submitted
- 26 Oct 2021
- Last updated
- 7 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33095849Giani 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.
PubMed 31045918Shum 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.
PubMed 24727536Schilder 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.
PubMed 25128022Stucker 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.
PubMed 25881975Giani 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.
PubMed 42088147
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy During Veno-venous ECMO: a Crossover Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT05148026
- Acronym / sponsor ID
- CRRT ECMO / 3732
- Conditions
- ARDS, Human, Acute Kidney Injury
- Keywords
- Extracorporeal Membrane Oxygenation, Acute Kidney Injury, ARDS, Renal Replacement Therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of Milano BicoccaUniversity, hospital or other
- Study start
- 14 Nov 2021 (actual)
- Primary completion
- 30 Jul 2025 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 8 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anticoagulation sequence 1 (UFH+ RCA) | Active comparator | Drug: Unfractionated heparin firstUFH+ RCA first |
| Anticoagulation sequence 2 (UFH) | Active comparator | Drug: Unfractionated heparin + RCA firstUFH first |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients admitted in ICU
- V-V ECMO support for acute respiratory failure
- CRRT therapy for acute kidney injury
Key exclusion criteria (4 listed)
- Pregnancy
- Pre-existing coagulation disorders
- Contraindication to heparin or citrate anticoagulation
- Moribund patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Unfractionated heparin + RCA firstAlso: Start with CVVHD, BF 100-120 ml/min, dialysate 2000 ml/h, RCA + systemic anticoagulationPatients are randomized to receive this sequence of anticoagulation regimens: UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA / UFH | Drug | Anticoagulation sequence 2 (UFH) |
| Unfractionated heparin firstAlso: Start with CVVHD, BF 200 ml/h, dialysate 2000 ml/h, systemic anticoagulation onlyPatients are randomized to receive this sequence of anticoagulation regimens: UFH / UFH+RCA / UFH / UFH+RCA / UFH / UFH+RCA | Drug | Anticoagulation sequence 1 (UFH+ RCA) |
Primary outcome
Incidence of CRRT circuit clotting according to anticoagulation regimen
Time frame: According to the manufacturer recommendation elective RRT circuit replacement will be performed after 72 hours of circuit life.
Rate of clotting in the intervention group (RCA+UFH) vs controls (UFH). I.e. : did the circuit clot in its 72h life?
4 secondary outcomes
CRRT circuit "survival" analysis
Time frame: 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
Time frame: 72 hours for each circuit
Incidence of citrate anticoagulation side-effects
Time frame: 72 hours for each circuit
To evaluate the anticoagulation effects of UFH and RCA
Time frame: 72 hours for each circuit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2026.
- Results publication: PubMed 33095849Zarbock 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 publication: PubMed 31045918Giani 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 publication: PubMed 24727536Shum 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 publication: PubMed 25128022Schilder 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 publication: PubMed 25881975Stucker 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.
- Derived from this study: PubMed 42088147Giani 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.
- Individual participant dataSharing planned: No
Related trials for ARDS, Human
Not yet recruitingObservational study
Early Switch in Moderate ARDS
Acute Respiratory Distress Syndrome (ARDS)
RecruitingPhase 3
Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen
Viral Lung Infection and Acute Respiratory Failure
Not yet recruitingPhase 2
Fostamatinib for Treating Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Adults
Acute Respiratory Distress Syndrome, ARDS
Not yet recruitingObservational study
Development and Prospective Validation of the AutoEIT Foundation Model for ARDS
ARDS (Acute Respiratory Distress Syndrome), Respiratory Failure
Not yet recruitingObservational study
Diaphragm Response in Elderly for Acute Monitoring
Acute Dyspnea, Acute Respiratory Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Unfractionated heparin + RCA first and Unfractionated heparin first in people with ARDS, Human and Acute Kidney Injury, run by University of Milano Bicocca at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of CRRT circuit clotting according to anticoagulation regimen (time frame: According to the manufacturer recommendation elective RRT circuit replacement will be performed after 72 hours of circuit life.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05148026, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2026.