Clinical trial NCT06224140: Heparin-Free Chronic HemoDialysis Assessment
Official title: Heparin-Free Chronic HemoDialysis Assessment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: End-Stage Renal Disease
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2024-01-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Intermittent hemodialysis is a complex technique which requires careful monitoring of anticoagulation levels to prevent clotting and reduce the risk of bleeding complications. Dialysis patients often exhibit hypercoagulable tendencies due to uremic state, turbulent blood flows in dialysis procedures, and thrombogenic exposure to artificial surfaces of dialysis tubing. Patients with ESRD may experience both dialyzer clotting and excessive bleeding, so individualized heparin dosing and periodic adjustments are necessary to ensure adequate anticoagulation during hemodialysis. The ideal anticoagulant should prevent thrombosis while minimizing the risk of intra- and interdialytic bleeding. The use of heparin carries risks such as worsening of osteoporosis and dyslipidemia, allergic reactions like pruritus, and the potential for life-threatening heparin-induced thrombocytopenia (HIT) for which avoidance of heparin is necessary during dialysis.Heparin, in both its unfractionated heparin (UFH) and low molecular weight heparin (LMWH) forms, is the most commonly used anticoagulant, though evidence comparing their efficacy and risk of bleeding remains inconclusive. End-stage renal disease (ESRD) patients, who are already at higher risk of serious bleeding, may benefit from regional anticoagulation (RA) techniques, as they typically receive around 600,000 IU of heparin per year. The investigators performed routinely a simplified regional anticoagulation procedure (RAP) using a constant calcium re-injection rate over the time to avoid hypocalcemia. This procedure eliminates the need for citrate infusion and calcium monitoring, and reduces nurse workload in a chronic dialysis unit. The investigators compared 21 chronic dialysis patients with 198 RA and 195 heparin sessions, where each patient acted as their own control. None of them were on VKA during the RA sessions, 62% were on single anti-platelet therapy and 14% were on dual anti-platelet therapy. The dialysis session success rate was 94% in the RA group and 97% in the heparin group, with no significant differences (p=0.22). The circuit loss rate was 1.5% per RA session and 0.5% per heparin session (p=0.23), and the early blood restitution rate was 3% and 1.5% (p=0.50) in the RA and heparin groups, respectively

Hypothesis: RAP can be as effective as systemic anticoagulation with heparin for intermittent dialysis in chronic hemodialysis patients, with the potential to reduce the rate of hemorrhagic events


Eligibility criteria: Inclusion Criteria:

* Man or woman aged 18 years or more
* Patients with end-stage renal disease (ESRD) under intermittent hemodialysis, for more than 3 months prior to screening and with a dialysis duration prescription of at least 4 hours
* Effective anticoagulation either by UFH or by LMWH of the dialysis session defined by the absence of circuit loss in the last 3 months.
* Dialysis adequacy defined by a mean Kt/V ≥1.2.
* Calcemia within the normal range at inclusion (2.2 to 2.6 mmol/L) (based on the results of the last monthly blood test)
* Subject affiliated to or beneficiary of a social security system.
* Subject having signed written informed consent.

Exclusion Criteria:

* Dysfunctional vascular access at the screening
* Unipunction of the AVF
* Patient treated by hemofiltration or hemodiafiltration procedure
* Current anticoagulation treatment
* Patient treated by digitalizing drugs
* Patient treated by thiazide diuretics
* Patient with hypercalcemia and/or hypercalciuria
* History of sensitivity to heparin or heparin-induced thrombocytopenia.
* Active hemorrhage
* High bleeding risk defined by the following situations: recent bleeding of less than 7 days, recent post-operative period of less than 7 days, recent head trauma of less than 7 days, recent ischemic stroke of less than 7 days, uremic pericarditis.
* Body weight \< 45 kg and \> 140 kg at screening.
* Known allergy to citrate
* Hospitalization at the screening for all other causes apart from dialysis
* Moribund status (defined by the expectation of death in less than three months).
* Liver failure (to prevent citrate liver toxicity) based on the results of the last monthly or quarterly blood test
* Ongoing participation in a concurrent interventional study in dialysis or with anti-coagulation therapy
* Pregnancy (declarative) or breastfeeding and all the other categories of people with special protection according to the French Code de la Santé Publique (CSP): patients under legal supervision, patients hospitalized without consent, patients admitted in social or sanitary structures for care and not research, and patients in emergency situations
* Patients unable to give an informed consent or unwilling to participate in the study.
* Heparin-coated membrane in current dialysis prescription

Primary outcomes:
measure: Demonstrate the non-inferiority of the regional anticoagulation procedure compared to heparin anticoagulation on the dialysis sessions success three times per week
timeFrame: 6 months
Secondary outcomes:
measure: Compare between the groups clinical Impact at each dialyses session on bypass loss
timeFrame: 6 months
measure: Compare between the groups clinical Impact at each dialyses session on early bypass restitution
timeFrame: 6 months
measure: Compare between the groups clinical Impact at each dialyses session on dialysis duration
timeFrame: 6 months
measure: Compare between the groups clinical Impact at each dialyses session on fistula compression time extended more than 10 minutes
timeFrame: 6 months
measure: Compare between the groups clinical Impact during the total duration of the study on incidence of hemorrhagic events
timeFrame: 6 months
measure: Compare between the groups clinical Impact during the total duration of the study on dialysis adequacy
timeFrame: 6 months
measure: Compare between the groups clinical Impact during the total duration of the study on relative effects on phosphocalcic balance
timeFrame: 6 months
measure: Compare between the groups clinical Impact during the total duration of the study on incidence of Hyperparthyroidism
timeFrame: 6 months
measure: Compare between the groups clinical Impact during the total duration of the study on incidence of non-hemorrhagic heparin-related complications
timeFrame: 6 months
measure: Compare between the groups clinical Impact during the total duration of the study on incidence of cardiovascular-related mortality and major cardiovascular events (MACE)
timeFrame: 6 months
measure: Compare between the groups clinical Impact during the total duration of the study on global mortality
timeFrame: 6 months
measure: Compare between the groups the tolerance of per-dialytic hypotension
timeFrame: 6 months
measure: Compare between the groups the tolerance of adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: Hôpital de la Conception
state: Bouches du Rhône
Study officials:
References: