A noninferiority trial comparing a heparin-grafted membrane plus citrate-containing dialysate versus regional citrate anticoagulation: Results of the CiTED study

Abstract

Background. Anticoagulation is a prerequisite for successful haemodialysis. Heparin and low-molecular weight heparins are routinely used despite increased bleeding risk. Regional citrate anticoagulation (RCA) is efficacious, but is laborious and may induce metabolic disturbances. Heparin-grafted membranes are less efficacious. It is not known whether combining citratecontaining dialysate and a heparin-grafted membrane is a valid anticoagulation strategy. Methods. We performed a randomized crossover noninferiority trial, with a prespecified noninferiority threshold of 10% in maintenance dialysis patients (n25). We compared the combination of citrate-containing dialysate plus a heparin-grafted membrane [CiTrate and EvoDial (CiTED) protocol] with RCA. The primary endpoint was completion of dialysis without significant clotting. Secondary endpoints included time to clotting, achieved Kt/Vurea, loss of total cell volume, venous air chamber clotting score and systemic-ionized calciumconcentration. Results. In total, 1284 sessions were performed according to study protocol, 636 in the CiTED arm and 648 in the RCA arm. The primary outcome of preterm interruption due to clotting occurred in 36 (5.7%) of sessions in the CiTED arm, and in 40 (6.2%) sessions in the RCA arm, thereby meeting noninferiority criteria (P<0.0001). Most of the clotting events occurred in the fourth hour of dialysis. Repetitive clotting occurred in four patients in the CiTED arm and one patient in the RCA arm. Time to preterm interruption due to clotting and achieved Kt/Vurea was not significantly different. Systemic-ionized calcium levels during treatment were significantly lower in the RCA arm and clinically relevant hypocalcaemia was noted only in the RCA arm. Conclusion. The combination of citrate-containing dialysate and a heparin-graftedmembrane is a valid alternative to RCA.