An Adjustable Dalteparin Sodium Dose Regimen for the Prevention of Clotting in the Extracorporeal Circuit in Hemodialysis: A Clinical Trial of Safety and Efficacy (the PARROT Study)

Abstract

Background: Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice.

Objective: The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week.

Design: A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016.

Setting: Ten sites in Canada.

Patients: A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week.

Measurements: The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation.

Methods: All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits.

Results: Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation.

Limitations: This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin <100 mg/d.

Conclusions: Overall, an adjustable dalteparin sodium dose regimen allowed safe completion of HD, with clinical benefits over fixed dosing.

Trial registration: ClinicalTrials.gov NCT01879618, registered June 13, 2013.

Keywords: adjustable dose; clinical study; dalteparin sodium; end-stage renal disease; hemodialysis.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SS, MA, SD, LR, NM, SC, MM, NP, BB, FM, and KT have no relationship with Pfizer other than being a site investigator in the PARROT study. JW has received consultancy fees from Pfizer in the past 3 years. FH, NS, KW, JO, and GF are full-time employees of Pfizer Inc and hold stock and/or stock options.

Figures

Figure 1.

Flow of participants through the study. aOther: surgery or renal transplant (3 participants); initiated peritoneal dialysis (1); changed hemodialysis session schedule (1); moved dialysis clinic (1); withdrawn owing to surgery (1); travel abroad (1). bOne participant had baseline data only.

Figure 2.

Dalteparin sodium doses administered. Note. HD = hemodialysis; IU = international units.

Figure 3.

Individual anti-Xa serum levels before HD at sessions 1, 10, and 20. Note. The bioaccumulation threshold for anti-Xa was 0.4 IU/mL and the lower limit of detection for anti-Xa was 0.04 IU/mL. HD = hemodialysis; IU = international units.