Sharpe 2020.

Study characteristics
Methods	Randomised controlled trial
Participants	Inclusion criteria: infants at risk of developing seizures or suspected of having seizures. Patients were term infants of a corrected gestational age between 36 and 44 weeks (< 2 weeks of age) with a weight of at least 2.2 kg. Exclusion criteria: (quote) "any previous ASMs (except short‐acting benzodiazepines administered for sedation > 24 hours before enrollment), if the serum creatinine level was > 1.6 mg/dL, or if seizures were due to correctable metabolic abnormalities (such as hypoglycaemia or hypocalcaemia). Patients in whom death was imminent were excluded. Patients in whom EEG monitoring could not be commenced before the need to treat definite clinical seizures were not recruited." LEV group, 64 patients HIE as seizure aetiology, n (%): 35 (55) Received hypothermia treatment, n (%): 24 (38) Male sex, n (%): 31 (48) Cord pH: n 31; Mean (SD): 7.07 (0.2) 5‐min Apgar score, n 64; mean (SD): 6.52 (3.01) Gestational age, n 64; mean (SD): wk 39.3 (1.3) Birth weight n 64; mean (SD): g 3342 (577) Pretreatment seizure severity n 52; mean (SD): min/h 12.3 (12.0) PB group, 42 patients HIE as seizure aetiology, n (%): 22 (52) Received hypothermia treatment, n (%): 18 (43) Male sex, n (%): 24 (57) Cord pH n 20, mean (SD): 7.15 (0.17) 5‐min Apgar score, n 40, mean (SD): 6.47 (2.4) Gestational age, n 42, mean (SD): wk 39.1 (1.3) Birth weight n 42, mean (SD): g 3317 (501) Pretreatment seizure severity, n 29, mean (SD): min/h 9.1 (9.3) The multicentre study was performed at hospitals in San Diego, USA; Oakland, USA, Auckland, New Zealand, and Loma Linda, USA. Patients were enrolled between March 2013 and October 2017.
Interventions	LEV: infusion over 15 minutes at 40 mg/kg, with an additional 15 minutes allowed for the medication to take effect. If electrographic seizures persisted or recurred 15 minutes after the first infusion was complete, an additional dose of the same treatment type was given. Patients who had received LEV at 40 mg/kg received an additional 20 mg/kg infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes after the second infusion was complete, the patient was then treated with the alternate treatment. Patients given any LEV loading doses received maintenance LEV at 10 mg/kg per dose, given IV every 8 hours for 5 days. PB: infusion over 15 minutes at 20 mg/kg, with an additional 15 minutes allowed for the medication to take effect. If electrographic seizures persisted or recurred 15 minutes after the first infusion was complete, an additional dose of the same treatment type was given. Patients who had received LEV at 20 mg/kg received an additional 20 mg/kg infusion over 15 minutes. If electrographic seizures persisted or recurred 15 minutes after the second infusion was complete, the patient was then treated with the alternate treatment. Patients given any PB loading doses received maintenance PB at 1.5 mg/kg per dose, given IV every 8 hours for 5 days.
Outcomes	Primary outcome: rate of achieving and maintaining electrographic seizure freedom for 24 hours Secondary outcomes: seizure cessation for 48 hours; rate of achieving and maintaining seizure freedom for 1 hour; subanalyses of the primary outcome measure for subjects with hypoxic‐ischaemic encephalopathy (HIE) who underwent therapeutic hypothermia
Notes	Funding: quote: "The NEOLEV2 study was funded by the US Food and Drug Administration Orphan Products Division (1 RO1FD004147). The Research Electronic Data Capture database is supported by National Institutes of Health Cooperative Agreement UL1TR001442. The Persyst EEG software company worked closely with the authors on the NEOLEV2 study and provided their software to the researchers free of charge, but have had no input into this article. The CortiCare commercial EEG monitoring company worked closely with the authors on the NEOLEV2 study on a commercial basis. They have had no input into the writing of this article. The authors of this article discussed the use of the automated neonatal seizure detection algorithm created by the Persyst EEG software company, which is not yet US Food and Drug Administration–approved for commercial use. Funded by the National Institutes of Health (NIH)." The authors reported not having potential conflicts of interest to disclose.