OC 06.1 - A pilot feasibility and safety multicenter trial of administering weight adjusted fixed dose of low molecular weight heparin (enoxaparin) to neonates and children with thrombosis (FIXET)

Background: Current guidelines recommend monitoring enoxaparin (most frequently used in neonates/children) using anti-Xa levels, despite little evidence for this approach. Routine monitoring is associated with discomfort from venipunctures and significant resource utilization.

Aims: To conduct pilot RCT evaluating feasibility and safety comparing approach of treating thrombosis in neonates/children with enoxaparin using weight-adjusted fixed dose to variable dose titrated to maintain pre-determined anti-Xa range (0.5-1.0 u/mL).

Methods: FIXET was prospective multicenter pilot RCT. Neonates/children 0-18 years old with VTE who met inclusion/exclusion criteria and provided informed consent were enrolled. Enoxaparin was initiated subcutaneous twice daily based on age as follows: 2.0mg/kg ( < 37 weeks CGA), 1.7mg/kg (≥37 weeks CGA - < 1m), 1.5mg/kg (1-2m), and 1.0mg/kg (>2 m). All patients were monitored with anti-Xa levels, but dose changes were level-based in control arm and weight-based in interventional arm. Treatment duration was up to discretion of treating physician. Primary outcomes were feasibility and safety (Table 1); secondary outcomes were resolution rate, mean anti-Xa levels, and number of dose-adjustments. Analysis was intention to treat using relevant statistical analysis based on data type.

Results: 21 patients recruited from 3 centers over 7 years; 20 eligible for analysis (1 undergoing treatment). Feasibility was not met as 5 subjects could not be recruited in all centers, but data collection and follow-up were 95% complete. Safety criteria met; 1 (5%) patient removed from study due to high anti-Xa level (1.22 u/mL), while there were no major bleeding episodes. Secondary outcomes were comparable between interventional and control arms (Table 2): complete resolution rate (55% vs 45%, p0.65), mean initial anti-Xa levels (0.57 vs 0.45, p0.27), and median number of dose adjustments per patient (2 vs 2, p0.82).

Conclusion(s): Weight-based dosing of enoxaparin was shown to be safe and have comparable efficacy in this pilot RCT. Larger studies are required to confirm this finding.