Blobner 2010.

Methods	Study design: phase 3A, European, 13‐centre, randomized, parallel‐group, comparative, active‐controlled, safety assessor‐blinded trial (the AURORA trial) Sample size calculation: powered to detect a difference ≥ 5 minutes from start of administration of sugammadex/neostigmine to TOFR > 0.9 between treatment groups
Participants	Number of randomized participants: 98 Inclusion criteria: ASA I to III, age ≥ 18 and of any body weight, scheduled for an elective surgical procedure under general anaesthesia Exclusion criteria: expected difficult intubation; receiving medication known to interact with rocuronium or vecuronium; having neuromuscular or significant renal disease, a history of malignant hyperthermia, an allergy, or other contraindication to medications used during the study; pregnant, potentially pregnant, or breastfeeding
Interventions	Anaesthesia: induced with propofol and maintained with sevoflurane NMBA: single intubating dose: rocuronium 0.6 mg/kg; maintenance dose: rocuronium 0.1 to 0.2 mg/kg Comparison: sugammadex 2.0 mg/kg (n = 49) vs neostigmine 50 µg/kg plus glycopyrrolate 10 µg/kg (n = 49) Administration time of sugammadex or neostigmine: reappearance of T2
Outcomes	Primary endpoint: time from start of administration of sugammadex/neostigmine to TOFR > 0.9 Secondary endpoint: time from start of administration of sugammadex/neostigmine to TOFR > 0.8 and 0.7 Other efficacy analysis: assessment of clinical signs of recovery (level of consciousness, 5 second head‐lift, general muscle weakness) Safety analysis: adverse events, serious adverse events, heart rate, blood pressure
Notes	Publication type: peer‐reviewed article Country: European study, 13 centres Conversions: Median + Range to Mean + SD following guidelines from Hozo 2005 Handling of adverse events: Data presented in Table 2 ‐ "Summary of the clinical signs of recovery and level of consciousness" ‐ regarding number of participants with muscle weakness and number of participants not able to perform 5 second head‐lift were considered to be adverse events in this review and were counted as such. Furthermore, study authors provided more detailed information regarding adverse events through email correspondence Authors' conclusions: Recovery of neuromuscular function after rocuronium to a TOFR = 0.9 is on average about 13 times faster with 2 mg/kg sugammadex than with 50 µg/kg neostigmine. Even more important, 98% of participants were sufficiently recovered within 5 minutes after sugammadex but 100 minutes after neostigmine before 98% of participants were sufficiently recovered. The safety profile did not differ between sugammadex‐treated and neostigmine‐treated patients Contact: First trial author Manfred Blobner contacted by email: blobner@lrz.tum.de; replied to questions regarding blinding of outcome assessor and referred to Tiffany Woo about questions regarding adverse events; replied 29.03.16 * Indicates unpublished data
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization codes were entered into a central randomization system ‐ part of a secured trial website. Enrolled participants were given a number in sequence of their enrolment and received a treatment code using the randomization system
Allocation concealment (selection bias)	Low risk	Central allocation (secondary to central randomization)
Blinding of participants (performance bias)	High risk	Open‐label study
Blinding of personnel (performance bias)	High risk	Open‐label study
Blinding of primary outcome assessment (detection bias)	Low risk	TOF‐watch assessor was blinded to treatment assignment*
Blinding of safety assessment (detection bias)	Low risk	Safety assessor was blinded to treatment assignment
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants are accounted for, and missing outcome data are balanced in numbers across intervention groups, with similar reasons for missing data across groups: 98 participants were enrolled ‐ 49 in the sugammadex group and 49 in the neostigmine group. One participant in each group did not receive study drug, and the all‐patients‐treated population included 48 participants in each group. All of these had ≥ 1 postbaseline efficacy measurement and, therefore, made up the intention‐to‐treat population
Selective reporting (reporting bias)	Low risk	Study protocol is available on clinicaltrials.gov (NCT00451217); all of the study's prespecified outcomes of interest to the review have been reported in the prespecified way
Funding bias	High risk	This work was supported by MSD, Oss, The Netherlands. M.B. and J.S. have received honoraria and travel grants from MSD within the past 3 years. L.I.E. is a scientific adviser to MSD and Abbott Scandinavia AB; his institution has received an institutional grant from MSD. M.E.P. is an employee of MSD. J.M. and G.D.R. have no conflicts of interest
Other bias	Low risk	Appears free of other sources of bias. Study sample size calculation designed to address this review's primary outcome. Treatment groups were mostly comparable in terms of their baseline characteristics and distribution of surgery types