Sugammadex for reversal of neuromuscular blockade in neonates and infants <2 years old: results from a phase IV randomized clinical trial.

Abstract

BACKGROUND Sugammadex is well-tolerated and effective for reversing neuromuscular blockade (NMB) in adults and children ≥2 years old. There is little information on its use in younger children. The aim of this study was to evaluate the efficacy and tolerability of sugammadex in children under 2 years of age. METHODS Phase IV, randomized, parallel-group, multicenter, clinical trial of sugammadex in participants aged birth to <2 years. Part A was open-label and included pharmacokinetic assessments to determine whether sugammadex dose-adjustment for Part B was necessary based on age. Part B was double-blind and evaluated sugammadex 2 mg/kg and 4 mg/kg. Participants were randomized to: 1) moderate NMB and reversal with 2 mg/kg sugammadex, or 2) moderate NMB and reversal with neostigmine + glycopyrrolate or atropine (hereafter, called neostigmine), or 3) deep NMB and reversal with 4 mg/kg sugammadex. The primary efficacy endpoint was time to neuromuscular recovery (TTNMR). The primary efficacy hypothesis was that sugammadex 2mg/kg would be superior to neostigmine for the reversal of moderate NMB as measured by TTNMR in Part B. RESULTS 138 participants aged 1 to 720 days were treated in Parts A+B (sugammadex 2mg/kg n=44, sugammadex 4 mg/kg n=63, neostigmine n=31). Based on pharmacokinetic assessments in Part A, no dose-adjustments for age were needed. In Part B, TTNMR for reversal of moderate NMB was faster with sugammadex 2 mg/kg than neostigmine (median of 1.4 minutes vs 4.4 minutes, hazard ratio = 2.40, 95% CI: 1.37, 4.18; p=0.0002). Sugammadex 4 mg/kg achieved rapid TTNMR for reversal of deep NMB with a median of 1.1 minutes (Parts A+B). The percentage of participants with ≥1 adverse event (Parts A+B) was similar for sugammadex and neostigmine. No deaths, drug-related serious adverse events, or hypersensitivity or anaphylaxis events were reported. CONCLUSIONS In children <2 years old, sugammadex 2 mg/kg reversed moderate NMB faster than neostigmine, and sugammadex 4 mg/kg rapidly reversed deep NMB. Sugammadex 2 mg/kg and 4 mg/kg were well-tolerated.