title: A prospective, randomized, multicentre trial for the treatment of refractory status epilepticus; experiences from evaluating the effect of the novel drug candidate, NS1209.
abstract: Refractory status epilepticus (RSE) is a life-threatening condition that requires immediate and aggressive treatment. Unfortunately, sometimes standard antiepileptic treatment is insufficient. Furthermore, alternative therapeutic options are limited by low evidence of efficacy. The primary objective of this study was to evaluate the effects of the novel drug candidate, NS1209 versus third-line standard treatment (phenytoin/valproate) for RSE. Having not reached the study end-points, the purpose of this paper is to discuss the challenges that are encountered in conducting a controlled study of RSE. This was a phase II, prospective, multicentre, single-blinded, randomized clinical trial and included patients to two separate protocols for convulsive and non-convulsive RSE (NS1209-006 and NS1209-007). In total, 28 patients were included and 14 patients were exposed to NS1209. At study conclusion, the study was insufficiently powered to detect any statistically significant difference between the two treatment groups. This was especially true for the convulsive RSE protocol. We conclude that high-quality studies in RSE are difficult to conduct owing to a number of ethical and practical problems associated with this critical illness. Challenges for further studies are discussed.
authors.affiliation: The Epilepsy Clinic, Department of Neurology, University State Hospital, Rigshospitalet, Copenhagen, Denmark. anne.sabers@rh.regionh.dk
authors.forename: Anne
authors.initials: A
authors.lastname: Sabers
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.forename: Arne
authors.initials: A
authors.lastname: Møller
authors.forename: Karen
authors.initials: K
authors.lastname: Rysgaard
authors.forename: Elinor
authors.initials: E
authors.lastname: Ben-Menachem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D004351:Drug Resistance; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D012107:Research Design; D013226:Status Epilepticus / Q000188:drug therapy* / Q000401:mortality; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D011758:Pyrroles; D018091:Receptors, AMPA; C119326:SPD 502; D044005:Tetrahydroisoquinolines
keywords: Controlled trial; NS1209; Refractory; Status epilepticus; Treatment