Sugammadex for Reversal of Neuromuscular Blockade in Neonates and Infants Less than 2 Years Old: Results from a Phase IV Randomized Clinical Trial.

Abstract

Sugammadex is well tolerated and effective for reversing neuromuscular blockade (NMB) in adults and children as young as 2 yr 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 yr of age. This was a phase IV, randomized, parallel-group, multicenter clinical trial of sugammadex in participants aged birth to less than 2 yr (NCT03909165). 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 doses of 2 and 4 mg/kg sugammadex. Participants were randomized to (1) moderate NMB and reversal with 2 mg/kg sugammadex; (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 2 mg/kg sugammadex would be superior to neostigmine for the reversal of moderate NMB as measured by TTNMR in part B. A total of 138 participants aged 1 to 720 days were treated in parts A and B (2 mg/kg sugammadex, n = 44; 4 mg/kg sugammadex, n = 63; and 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 2 mg/kg sugammadex than neostigmine (median of 1.4 min vs. 4.4 min; hazard ratio, 2.40; 95% CI, 1.37 to 4.18; P = 0.0002). A 4-mg/kg dose of sugammadex achieved rapid TTNMR for reversal of deep NMB with a median of 1.1 min (parts A and B). The percentage of participants with one or more adverse events (parts A and B) was similar for sugammadex and neostigmine. No deaths, drug-related serious adverse events, or hypersensitivity or anaphylaxis events were reported. In children less than 2 yr old, 2 mg/kg sugammadex reversed moderate NMB faster than neostigmine, and 4 mg/kg sugammadex rapidly reversed deep NMB. Sugammadex doses of 2 and 4 mg/kg were well tolerated.