SP481DALTEPARIN SODIUM FOR THE PREVENTION OF CLOTTING IN THE EXTRACORPOREAL CIRCUIT DURING HEMODIALYSIS: A PHASE IIIB OPEN-LABEL STUDY TO OPTIMIZE A SINGLE BOLUS DOSE—THE PARROT STUDY

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INTRODUCTION AND AIMS: Dalteparin sodium, a low-molecular weight heparin (LMWH), is indicated for prevention of clotting in the extracorporeal system during hemodialysis (HD). Product labelling recommends a fixed, single bolus dose of 5000 international units (IU) for HD sessions lasting <4 hours. However, flexible dosing above or below 5000 IU may be beneficial. The aim of this study was to investigate the safety and efficacy of dalteparin sodium during HD, using a flexible-dose regimen. METHODS: This was a single-arm study of patients with chronic renal failure who require 3-4 HD sessions per week lasting up to 4 hours per session, previously receiving unfractionated heparin or LMWHs. Participants received a bolus of dalteparin sodium 5000 IU, administered into the arterial side of the dialysis circuit. Dalteparin sodium dose could be adjusted (+/- 500 or 1000 IU) at subsequent HD sessions (<20 sessions) when clinically indicated, with no specified dose limits. The primary efficacy endpoint was the proportion of successful HD sessions, defined as an HD session that was conducted without termination due to clotting. Fixed and flexible dosing regimens were compared using a split-sample statistical approach. RESULTS: Of a total 2827 HD sessions (152 participants; mean age, 57.1 years; 69.7% male), 2776 (98.2%) were evaluable for efficacy, and 2774 were successful (99.9%; [95% CI: 99.7, 100]). A total of 79 participants (52.3%) received ≥1 dose adjustment (average dose, 5488 IU; range, 500-13,000 IU), mostly due to clotting or access compression time >10 minutes. The median difference in the proportion of successful HD sessions between the fixed and flexible dosing regimens was −0.1% (95% CI: −0.3%, 0.1%). Grade 3 and 4 clotting occurred in 402 (14.5%) and 77 (2.8%) HD sessions, respectively. Of 2818 (99.7%) HD sessions evaluable for safety, 65 (2.3%) were associated with minor bleeding, and 1 (0.04%) with a clinically relevant non-major bleed. There were no major bleeds or deaths reported during the study. CONCLUSIONS: A flexible dalteparin sodium dosing regimen was safe and effective in patients with chronic renal failure requiring 3-4 HD session per week, and may have clinical benefits over the standard fixed-dose regimen for preventing clotting in the extracorporeal circuit during HD.

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