Hemodialysis ComplicationPhase 2C2DNCT03842657
Regional Anticoagulation of Dialysis Circuits With a Calcium-free Citrate-containing Dialysate
A Phase 2 study testing anticoagulation of the dialysis circuit in people with Hemodialysis Complication and Bleeding, run by University Hospital, Toulouse at 5 sites in France.
Trial summary
Critically ill patients have a high risk of bleeding but also require prolonged intermittent dialysis. Thus, a heparin-free easy-to-use alternative type of anticoagulation within the dialysis circuit is required. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemodialysis Complication, Bleeding
- What is being tested?
- anticoagulation of the dialysis circuit
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 5 sitesFrance
- Study dates
- 5 Jul 2019to 13 Sep 2021
- Phase
- Phase 2
- 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
- hat require two sessions of dialysis that last for greater than 240 minutes in the 7 days following the inclusion.
- With a moderate to high risk of bleeding (platelets count below 150.000/mm3; platelet disorders; bleeding in the last 10 days, surgery or biopsy in the last 10 days or planned in the next 7 days; admission to the ICU)
- Older than 18 years of age
- That gave written informed consent
- Exclusion Criteria: will be excluded from the study, patients with
- Heparin allergy
Show all 11Show fewer
- On-going treatment by vitamin-K antagonists (INR > 1.2) or unfractionated heparin (anti-Xa activity > 0.10)..
- Known allergy to the Evodial (Baxter, France) or Cordiax FX100 (Fresenius, France) membranes
- On-going treatment by angiotensin converting enzyme inhibitors
- Pregnancy or risk of pregnancy
- Patient under guardianship
Who cannot join
None listed.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
Pellegrin Hospital
Bordeaux
Montpellier Hospital
Montpellier
Nimes Hospital
Nîmes
Tenon Hospital
Paris
CHU Toulouse
Toulouse
About this study
Official title: Regional Anticoagulation of Dialysis Extra-corporeal Circuits With a Calcium-free Citrate-containing Dialysate : Efficiency and Tolerance
Critically ill patients have a high risk of bleeding but also require prolonged intermittent dialysis. Thus, a heparin-free easy-to-use alternative type of anticoagulation within the dialysis circuit is required. In a non-comparative study, heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance, was considered as safe and efficient. The aim of this study is to confirm the superiority of this approach compared to a anticoagulation based on heparin-grafted membrane.
Read the detailed description
Critically ill patients have a high risk of bleeding but also require prolonged intermittent dialysis. Several modalities are used for heparin-free dialysis sessions. Iterative saline infusion and heparin-grafted membranes are easy to use and remain the standards-of-care for high-risk bleeding situations but efficiency is low: success rates from hemodialysis sessions range from 50% to 65% and 50% to 75%, respectively. Furthermore, sessions that last for greater than 240 minutes are rarely achievable and can be problematic when ensuring an adequate dose of dialysis and a negative water balance in patients who cannot tolerate a high ultrafiltration rate. Thus, the development of alternative regional anticoagulation methods is needed urgently to improve intermittent hemodialysis (IHD) in critically ill patients and to avoid systemic anticoagulation in patients with a high risk of bleeding.
An easy way to provide citrate inside the filter, to lower iCa below 0.45 mmol/L could be to use diffusive influx from the dialysate. It has been demonstrated recently that the use of citric acid as the acidic component of dialysate can enable a dose reduction of heparin and increase the efficiency of hemodialysis. However, the amount of citrate (0.8 mmol/L) and calcium (1.25-1.75 mmol/L) contained in this dialysate do not allow the target of iCa to be reached in the ECC. In contrast, a citrate dialysate that contains no calcium would provide enough calcium-free transfer to lower iCa below 0.45 mmol/L; however, a problem would be the large amount of calcium loss during the session.
Pivotal studies show that, during dialysis sessions performed with calcium-free dialysate, the rate of calcium reinjection required to compensate for calcium loss in the dialysate can be easily deducted from the ionic dialysance (ID), which is an online measurement of instantaneous small solute clearance, available from most dialysis monitors. ID has been also used as a surrogate marker for dialysis dose in ICU patients receiving IHD. Thus, the use of calcium-free citrate-containing dialysate with calcium reinjection according to ID could provide enough citrate to prevent coagulation within the filter, and calcium restitution can then be monitored by online ID without the need for systemic measurement of iCa. It may also improve the hemodynamic tolerance of IHD by avoiding acetate in the dialysate.
The objective of the present study was to show the efficiency of this approach using RCA for dialysis sessions (<4 hrs) of IHD in patients with moderate to high risk of bleeding, based on the success rate of hemodialysis without clotting. Each patient included in this study will receive two heparin-free dialysis sessions with heparin-grafted membrane (control group) or RCA with calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance (experimental group), alternatively. The order of anticoagulation will be randomized.
- Conditions
- Hemodialysis Complication, Bleeding
- Being tested
- anticoagulation of the dialysis circuit
- Keywords
- citrate, dialysate, hemodialysis, coagulation
- Medical subject headings
- Hemorrhage, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anticoagulation of the dialysis circuitCombination product
Each patient included in this study will receive two heparin-free dialysis sessions with heparin-grafted membrane (control group) or RCA with calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance (experimental group), alternatively
| Study group | Role | What they receive |
|---|---|---|
| calcium-free citrate-containing dialysate | Other | Dialysis session will be performed with a non-heparin grafted membrane, a dialysate without calcium (0 mmol/L) and citrate 0.8 mmol/L, a reinjection of a calcium solution (300 mM) according to the ionic dialysance, and no heparin addition Receives: Combination Product: anticoagulation of the dialysis circuit |
| heparin-grafted membrane | Other | dialysis session will be performed with a heparin-grafted membrane, a dialysate with calcium (1.65 mmol/L) and citrate 0.8 mmol/L, and no heparin addition Receives: Combination Product: anticoagulation of the dialysis circuit |
What is being measured
The primary outcome is the main question the study is designed to answer.
Premature termination of the first dialysis session (<4 hours) related to a coagulation of the dialysis circuit
Premature termination of the dialysis session (<4 hours) in connection with coagulation or pre-coagulation state of the dialysis circuit (thrombosis global index strictly greater than 1 (visual assessment) or elevation of transmembrane pressure above 350 mmHg)
Measured: Visite T1 (3 days maximum after inclusion visit)
Premature termination of the second dialysis session (<4 hours) related to a coagulation of the dialysis circuit
Premature termination of the dialysis session (<4 hours) in connection with coagulation or pre-coagulation state of the dialysis circuit (thrombosis global index strictly greater than 1 (visual assessment) or elevation of transmembrane pressure above 350 mmHg)
Measured: Visite T2 (7 days maximum after inclusion visit)
Secondary outcomes (4)
Hemodynamic tolerance
Number of cardiovascular events during the dialysis session
Measured: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit)
Clinical tolerance
Clinical symptoms collected every 30 min on patient
Measured: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit)
Biological tolerance
Measurement of total and ionized calcium and venous pH sampled on the arterial branch of the dialysis circuit
Measured: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit)
Systemic inflammation
To determine the serum levels of cytokines (interleukine-6, interferon-γ, MCP1, Tumor Necrosis Factor-α) by ELISA.
Measured: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start5 Jul 2019
- Primary completion13 Sep 2021
- Study completion13 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemodialysis ComplicationStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stanislas FAGUER, MD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03842657
- Sponsor's protocol ID
- RC31/17/0451
- Acronym
- C2D
- Status last verified
- Mar 2022
- First submitted
- 29 Jan 2019
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Faguer S, Serre JE, Brusq C, Bongard V, Casemayou A, Moranne O, Pfirmann P, Rafat C, Cointault O. A randomized crossover trial of regional anticoagulation modalities for intermittent haemodialysis. Nephrol Dial Transplant. 2025 Feb 28;40(3):537-543. doi: 10.1093/ndt/gfae155.
PubMed 38977911
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regional Anticoagulation of Dialysis Extra-corporeal Circuits With a Calcium-free Citrate-containing Dialysate : Efficiency and Tolerance
- ClinicalTrials.gov ID
- NCT03842657
- Acronym / sponsor ID
- C2D / RC31/17/0451
- Conditions
- Hemodialysis Complication, Bleeding
- Keywords
- citrate, dialysate, hemodialysis, coagulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 5 Jul 2019 (actual)
- Primary completion
- 13 Sep 2021 (actual)
- Study completion
- 13 Sep 2021 (actual)
- First posted
- 15 Feb 2019 (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.
Critically ill patients have a high risk of bleeding but also require prolonged intermittent dialysis. Thus, a heparin-free easy-to-use alternative type of anticoagulation within the dialysis circuit is required. In a non-comparative study, heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance, was considered as safe and efficient. The aim of this study is to confirm the superiority of this approach compared to a anticoagulation based on heparin-grafted membrane.
Detailed description
Critically ill patients have a high risk of bleeding but also require prolonged intermittent dialysis. Several modalities are used for heparin-free dialysis sessions. Iterative saline infusion and heparin-grafted membranes are easy to use and remain the standards-of-care for high-risk bleeding situations but efficiency is low: success rates from hemodialysis sessions range from 50% to 65% and 50% to 75%, respectively. Furthermore, sessions that last for greater than 240 minutes are rarely achievable and can be problematic when ensuring an adequate dose of dialysis and a negative water balance in patients who cannot tolerate a high ultrafiltration rate. Thus, the development of alternative regional anticoagulation methods is needed urgently to improve intermittent hemodialysis (IHD) in critically ill patients and to avoid systemic anticoagulation in patients with a high risk of bleeding.
An easy way to provide citrate inside the filter, to lower iCa below 0.45 mmol/L could be to use diffusive influx from the dialysate. It has been demonstrated recently that the use of citric acid as the acidic component of dialysate can enable a dose reduction of heparin and increase the efficiency of hemodialysis. However, the amount of citrate (0.8 mmol/L) and calcium (1.25-1.75 mmol/L) contained in this dialysate do not allow the target of iCa to be reached in the ECC. In contrast, a citrate dialysate that contains no calcium would provide enough calcium-free transfer to lower iCa below 0.45 mmol/L; however, a problem would be the large amount of calcium loss during the session.
Pivotal studies show that, during dialysis sessions performed with calcium-free dialysate, the rate of calcium reinjection required to compensate for calcium loss in the dialysate can be easily deducted from the ionic dialysance (ID), which is an online measurement of instantaneous small solute clearance, available from most dialysis monitors. ID has been also used as a surrogate marker for dialysis dose in ICU patients receiving IHD. Thus, the use of calcium-free citrate-containing dialysate with calcium reinjection according to ID could provide enough citrate to prevent coagulation within the filter, and calcium restitution can then be monitored by online ID without the need for systemic measurement of iCa. It may also improve the hemodynamic tolerance of IHD by avoiding acetate in the dialysate.
The objective of the present study was to show the efficiency of this approach using RCA for dialysis sessions (<4 hrs) of IHD in patients with moderate to high risk of bleeding, based on the success rate of hemodialysis without clotting. Each patient included in this study will receive two heparin-free dialysis sessions with heparin-grafted membrane (control group) or RCA with calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance (experimental group), alternatively. The order of anticoagulation will be randomized.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| calcium-free citrate-containing dialysate | Other | Combination Product: anticoagulation of the dialysis circuitDialysis session will be performed with a non-heparin grafted membrane, a dialysate without calcium (0 mmol/L) and citrate 0.8 mmol/L, a reinjection of a calcium solution (300 mM) according to the ionic dialysance, and no heparin addition |
| heparin-grafted membrane | Other | Combination Product: anticoagulation of the dialysis circuitdialysis session will be performed with a heparin-grafted membrane, a dialysate with calcium (1.65 mmol/L) and citrate 0.8 mmol/L, and no heparin addition |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- hat require two sessions of dialysis that last for greater than 240 minutes in the 7 days following the inclusion.
- With a moderate to high risk of bleeding (platelets count below 150.000/mm3; platelet disorders; bleeding in the last 10 days, surgery or biopsy in the last 10 days or planned in the next 7 days; admission to the ICU)
- Older than 18 years of age
- That gave written informed consent
- Exclusion Criteria: will be excluded from the study, patients with
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| anticoagulation of the dialysis circuitEach patient included in this study will receive two heparin-free dialysis sessions with heparin-grafted membrane (control group) or RCA with calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance (experimental group), alternatively | Combination product | calcium-free citrate-containing dialysate, heparin-grafted membrane |
Primary outcome
Premature termination of the first dialysis session (<4 hours) related to a coagulation of the dialysis circuit
Time frame: Visite T1 (3 days maximum after inclusion visit)
Premature termination of the dialysis session (<4 hours) in connection with coagulation or pre-coagulation state of the dialysis circuit (thrombosis global index strictly greater than 1 (visual assessment) or elevation of transmembrane pressure above 350 mmHg)
Premature termination of the second dialysis session (<4 hours) related to a coagulation of the dialysis circuit
Time frame: Visite T2 (7 days maximum after inclusion visit)
Premature termination of the dialysis session (<4 hours) in connection with coagulation or pre-coagulation state of the dialysis circuit (thrombosis global index strictly greater than 1 (visual assessment) or elevation of transmembrane pressure above 350 mmHg)
4 secondary outcomes
Hemodynamic tolerance
Time frame: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit)
Clinical tolerance
Time frame: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit)
Biological tolerance
Time frame: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit)
Systemic inflammation
Time frame: Visite T1 (3 days maximum after inclusion visit), Visite T2 (7 days maximum after inclusion visit)
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 15 Dec 2025.
- Results publication: PubMed 38977911Faguer S, Serre JE, Brusq C, Bongard V, Casemayou A, Moranne O, Pfirmann P, Rafat C, Cointault O. A randomized crossover trial of regional anticoagulation modalities for intermittent haemodialysis. Nephrol Dial Transplant. 2025 Feb 28;40(3):537-543. doi: 10.1093/ndt/gfae155.
- Individual participant dataSharing planned: No
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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.
Stanislas FAGUER, MD principal investigator
University Hospital, Toulouse
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing anticoagulation of the dialysis circuit in people with Hemodialysis Complication and Bleeding, run by University Hospital, Toulouse at 5 sites in France.
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 11 inclusion and 0 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 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Premature termination of the first dialysis session (<4 hours) related to a coagulation of the dialysis circuit (time frame: Visite T1 (3 days maximum after inclusion visit)). The study lists 2 primary outcomes in all. 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 NCT03842657, which also lists 1 linked publication.
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 15 Dec 2025.