10.6084/m9.figshare.8131547.v1 Nuñez-Ramiro A. Nuñez-Ramiro A. Benavente-Fernández I. Benavente-Fernández I. Valverde E. Valverde E. Cordeiro M. Cordeiro M. Blanco D. Blanco D. Boix H. Boix H. Cabañas F. Cabañas F. Chaffanel M. Chaffanel M. Fernández-Colomer B. Fernández-Colomer B. Fernández-Lorenzo J.R. Fernández-Lorenzo J.R. Kuligowski J. Kuligowski J. Loureiro B. Loureiro B. Moral-Pumarega M.T. Moral-Pumarega M.T. Pavón A. Pavón A. Sánchez-Illana A. Sánchez-Illana A. Tofé I. Tofé I. Hervás D. Hervás D. García-Robles A. García-Robles A. Parra-Llorca A. Parra-Llorca A. Cernada M. Cernada M. Martinez-Rodilla J. Martinez-Rodilla J. Lorente-Pozo S. Lorente-Pozo S. Llorens R. Llorens R. Marqués R. Marqués R. Vento M. Vento M. on behalf of the Hypotop Study Group on behalf of the Hypotop Study Group Supplementary Material for: Topiramate plus Cooling for Hypoxic-Ischemic Encephalopathy: A Randomized, Controlled, Multicenter, Double-Blinded Trial Karger Publishers 2019 Hypoxic-ischemic encephalopathy Seizures Hyperexcitability Anaerobic metabolism Oxidative stress biomarkers 2019-05-15 09:21:48 Dataset https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Topiramate_plus_Cooling_for_Hypoxic-Ischemic_Encephalopathy_A_Randomized_Controlled_Multicenter_Double-Blinded_Trial/8131547 <b><i>Background and Objectives:</i></b> Therapeutic interventions to improve the efficacy of whole-body cooling for hypoxic-ischemic encephalopathy (HIE) are desirable. Topiramate has been effective in reducing brain damage in experimental studies. However, in the clinical setting information is limited to a small number of feasibility trials. We launched a randomized controlled double-blinded topiramate/placebo multicenter trial with the primary objective being to reduce the antiepileptic activity in cooled neonates with HIE and assess if brain damage would be reduced as a consequence. <b><i>Study Design:</i></b> Neonates were randomly assigned to topiramate or placebo at the initiation of hypothermia. Topiramate was administered via a nasogastric tube. Brain electric activity was continuously monitored. Topiramate pharmacokinetics, energy-related and Krebs’ cycle intermediates, and lipid peroxidation biomarkers were determined using liquid chromatography-mass spectrometry and MRI for assessing brain damage. <b><i>Results:</i></b> Out of 180 eligible patients 110 were randomized, 57 (51.8%) to topiramate and 53 (48.2%) to placebo. No differences in the perinatal or postnatal variables were found. The topiramate group exhibited less seizure burden in the first 24 h of hypothermia (topiramate, <i>n</i> = 14 [25.9%] vs. placebo, <i>n</i> = 22 [42%]); needed less additional medication, and had lower mortality (topiramate, <i>n</i> = 5 [9.2%] vs. placebo, <i>n</i> = 10 [19.2%]); however, these results did not achieve statistical significance. Topiramate achieved a therapeutic range in 37.5 and 75.5% of the patients at 24 and 48 h, respectively. A significant association between serum topiramate levels and seizure activity (<i>p</i> < 0.016) was established. No differences for oxidative stress, energy-related metabolites, or MRI were found. <b><i>Conclusions:</i></b> Topiramate reduced seizures in patients achieving therapeutic levels in the first hours after treatment initiation; however, they represented only a part of the study population. Our results warrant further studies with higher loading and maintenance dosing of topiramate.