JMIR Publications

ABSTRACT

Background:

Generalized convulsive status epilepticus (GCSE) is a frequent medical emergency. Treatment focuses on administration of benzodiazepines followed by a second line antiepileptic drug (AED). Despite this stepwise strategy, GCSE is not controlled in a quarter of patients and is associated with protracted hospitalization, high-mortality and long-term disability.

Objective:

We aimed to show that the administration of valproic acid (VPA) may be suited as a complement of the first and second-line treatment, because of antiepileptic efficacy, neuroprotective properties and good tolerability.

Methods:

We conducted a multicenter, double-blind, randomized controlled trial comparing VPA to placebo in adults admitted to intensive care units (ICU) for GCSE in France. All patients received standard of care including a benzodiazepine and a second-line AED (except VPA) at the discretion of the treating medical team. In the intervention arm, VPA was administered intravenously as a loading dose of 30mg/kg over 15 minutes followed by a continuous infusion of 1 mg/kg/h over the next 12 hours. In the placebo group, an identical IV administration of 0.9 % saline was used. The primary outcome was the proportion of patients discharged alive from hospital by day 15. Secondary outcomes were frequency of refractory and super-refractory GCSE; ICU-related morbidity; adverse events related to VPA, and cognitive dysfunction at 3 months. Statistical analyses will be performed according to the intent-to-treat principle. Ethics Committee of Saint-Germain-en-Laye, France, initial approval received on May 14 2012. Results will be disseminated via peer-reviewed publication and presentation at international conferences.

Results:

The first patient was randomized on February 18, 2013 and the last patient on July 7, 2018. 245 (99%) out of 248 planned patients were enrolled across 20 ICUs. At present, data management is still ongoing, and all parties involved in the trial remain blinded.Research

Conclusions:

This is the first multicentre randomized double-blind controlled trial that assesses whether Valproic Acid can be useful as an adjuvant therapy to recommended first and second line anti-epileptic drugs for improving the outcome of GCSE. Clinical Trial: NCT01791868 (registered on May 2012).