Regional Anticoagulation of Dialysis Circuits With a Calcium-free Citrate-containing Dialysate

NCT ID: NCT03842657

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-05
• Study Completion Date: 2021-09-13

Brief 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. 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.

Conditions

Hemodialysis Complication; Bleeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

calcium-free citrate-containing dialysate

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

Group Type: OTHER

anticoagulation of the dialysis circuit

Intervention Type: COMBINATION_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

heparin-grafted membrane

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

Group Type: OTHER

anticoagulation of the dialysis circuit

Intervention Type: COMBINATION_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

Interventions

anticoagulation of the dialysis circuit

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

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• 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

• Heparin allergy
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stanislas FAGUER, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

Pellegrin Hospital

Bordeaux, , France

Montpellier Hospital

Montpellier, , France

Nimes Hospital

Nîmes, , France

Tenon Hospital

Paris, , France

CHU Toulouse

Toulouse, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 38977911 (View on PubMed)

Other Identifiers

RC31/17/0451

Identifier Type: -

Identifier Source: org_study_id