Dialyzer Performance During Hemodialysis Without Systemic Anticoagulation Using a Heparin-Grafted Dialyzer Combined With a Citrate-Enriched Dialysate: Results of the Randomized Crossover Noninferiority EvoCit Study

Abstract

Rationale & objective: The EvoCit study was designed to evaluate performance of a heparin-grafted dialyzer during hemodialysis with and without systemic anticoagulation.

Study design: Randomized, crossover, noninferiority trial. Noninferiority was defined as a difference of≤10% for the primary outcome.

Setting & participants: Single hemodialysis center; 26 prevalent patients treated with 617 hemodialysis sessions.

Interventions: Hemodialysis using a heparin-grafted dialyzer combined with a 1.0mmol/L citrate-enriched dialysate ("EvoCit") without systemic anticoagulation compared with hemodialysis performed with a heparin-grafted dialyzer with systemic heparin ("EvoHep"). Patients were randomly allocated to a first period of 4 weeks and crossed over to the alternative strategy for a second period of 4 weeks.

Outcomes: The primary end point was the difference in Kt/V_urea between EvoCit and EvoHep. Secondary end points were urea reduction ratio, middle molecule removal, treatment time, thrombin generation, and reduction in dialyzer blood compartment volume.

Results: The estimated difference in Kt/V_urea between EvoCit and EvoHep was-0.03 (95% CI, -0.06 to-0.007), establishing noninferiority with mean Kt/V_urea of 1.47±0.05 (SE) for EvoCit and 1.50±0.05 for EvoHep. Noninferiority was also established for reduction ratios of urea and β₂-microglobulin. Premature discontinuation of dialysis was required for 4.2% of sessions among 6 patients during EvoCit and no sessions during EvoHep. Effective treatment time was 236±5 minutes for EvoCit and 238±1 minutes for EvoHep. Thrombin generation was increased and there was greater reduction in dialyzer blood compartment volume after treatments with EvoCit compared with EvoHep.

Limitations: The effects of avoiding systemic anticoagulation on clinical outcomes were not evaluated.

Conclusions: EvoCit is noninferior to EvoHep with respect to solute clearance but results in a greater number of shortened treatments, more membrane clotting, and greater thrombin generation TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03887468.

Keywords: Anticoagulation; bleeding risk; blood compartment volume; clotting; dialysis adequacy; dialysis dose; end-stage renal disease (ESRD); extracorporeal circuit; heparin-free hemodialysis; noninferiority trial; randomized crossover study; systemic anticoagulation; thrombin generation; treatment length.