Valproic Acid as Adjuvant Treatment for Convulsive Status Epilepticus: a Randomised Clinical Trial (original) (raw)
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JMIR Research Protocols
Background: Generalized convulsive status epilepticus (GCSE) is a frequent medical emergency. GCSE treatment focuses on the administration of benzodiazepines followed by a second-line antiepileptic drug (AED). Despite this stepwise strategy, GCSE is not controlled in one-quarter of patients and is associated with protracted hospitalization, high mortality, and long-term disability. Valproic acid (VPA) is an AED with good tolerability and neuroprotective properties. Objective: This study aims to demonstrate that administration of VPA as an adjuvant for first-and second-line treatment in GCSE can improve outcomes. Methods: A multicenter, double-blind, randomized controlled trial was conducted, comparing VPA with a placebo in adults admitted to intensive care units (ICUs) for GCSE in France. GCSE was diagnosed by specifically trained ICU physicians according to standard criteria. All patients received standard of care, including a benzodiazepine and a second-line AED (not VPA), at the discretion of the treating medical team. In the intervention arm, VPA was administered intravenously at a loading dose of 30 mg/kg over 15 minutes, followed by a continuous infusion of 1 mg/kg/hour over the next 12 hours. In the placebo group, an identical intravenous administration of 0.9% saline was used. The primary outcome was the proportion of patients discharged alive from the 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. Results: The first patient was randomized on February 18, 2013, and the last patient was randomized on July 7, 2018. Of 248 planned patients, 98.7% (245/248) were enrolled across 20 ICUs. At present, data management is still ongoing, and all parties involved in the trial remain blinded. Conclusions: The Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus (VALSE) trial will evaluate whether the use of VPA as an adjuvant for first-and second-line treatment in GCSE improves outcomes.
Efficacy and safety of intravenous valproate for status epilepticus: a systematic review
2014
Introduction The effectiveness of valproate (VPA) in the treatment of focal and generalized epilepsies is well established. The drug has a wide spectrum of action, good tolerability, and has been available as an injectable formulation since 1993. Despite the lack of class A evidence, it has been used extensively in various forms of status epilepticus (SE). Aim Our aim was to present a systematic review of data from randomized and non-randomized controlled trials to evaluate the efficacy and safety of intravenous VPA for the treatment of SE. Methods Data sources included MEDLINE, back tracing of references in pertinent studies, and contact with the manufacturer of VPA (Sanofi-Aventis).
IV Valproate in generalized convulsive status epilepticus: a systematic review
European Journal of Neurology, 2012
Aim of this review was to evaluate efficacy and safety of intravenous valproate (IV VPA) in the treatment of generalized convulsive status epilepticus (GCSE) in patients of any age, synthesizing available evidences from randomized controlled trials (RCTs). RCTs on IV VPA administered in patients (no age restriction) for GCSE at any stage were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. Studies were selected and data independently extracted. Following outcomes were considered: clinical seizure cessation after drug administration, seizure freedom at 24 h, and adverse effects. Outcomes were assessed using standard methods to calculate risk ratio (RR) with 95% confidence intervals. Five trials met inclusion criteria. Two different comparisons were available (IV VPA versus phenytoin (PHT), IV VPA versus IV Diazepam), but only the former included more than one study with enough information to permit a meta-analysis. Compared with PHT, VPA had statistically lower risk of adverse effects (RR 0.31, 95% CI 0.12-0.85), with no differences in GCSE cessation after drug administration (RR 1.31, 95% CI 0.93-1.84) and in seizure freedom at 24 h (RR 0.96, 95% CI 0.88-1.06). This review suggests that IV VPA has a better tolerability than PHT in treatment of GCSE, without any statistically significant differences in terms of efficacy. More rigorous RCTs of VPA versus an appropriate comparator, in a well-defined population with a systematic definition of SE, are however required to conclude about efficacy and tolerability of VPA in clinical practice.
Serum concentrations of valproic acid in people with epilepsy: Clinical implication
Journal of Pharmacy & Pharmacognosy Research, 2022
Context: Therapeutic drug monitoring (TDM) allows personalizing the dose of valproic acid in patients with epilepsy to optimize drug therapy, minimize adverse effects and detect interactions. Aims: To determine valproic acid concentrations in serum samples from people with epilepsy and to analyze its clinical implications. Methods: Cloned donor enzyme immunoassay; descriptive, cross-sectional, non-randomized, convenience recruitment study of 57 voluntary patients with epilepsy (n = 39 male, 68.42%; n = 18 female, 31.58%) aged between 19 and 62 years. After three months of treatment with valproic acid, a single blood sample was collected from each volunteer at a minimal concentration. Results: Serum drug concentrations 51.30-100.10 mg/L (SD 5.94) and level/dose 2.17-5.31 (SD 1.14) were observed. Association was shown between the dose ratio/dose of valproic acid (R 2 = 0.8693; p<0.05) and the Mann-Whitney U test (p<0.05). Valproic acid monotherapy and association with carbamazepine and phenytoin are not different between treatment groups (Mann-Whitney U test: p = 0.391 > α = 0.05). Conclusions: Serum valproic acid concentrations are within the therapeutic range, and there is a significant inverse linear correlation between dose ratio/dose, which must be considered to personalize the dose and optimize the pharmacotherapeutic result.
Factors Associated with Good Seizure Control in Patients on Valproic Acid
The Eurasian Journal of Medicine
Aims and Scope Eurasian Journal of Medicine (Eurasian J Med) is an international, scientific, open access periodical published by independent, unbiased, and triple-blinded peer-review principles. The journal is the official publication of Atatürk University School of Medicine and published triannually in February, June, and October. The publication language of the journal is English. The aim of the Eurasian Journal of Medicine is to publish original research papers of the highest scientific and clinical value in all medical fields. The Eurasian J Med also includes reviews, editorial short notes and letters to the editor that either as a comment related to recently published articles in our journal or as a case report. The target audience of the journal includes researchers, physicians and healthcare professionals who are interested or working in in all medical disciplines.
Background: Status epilepticus (SE) is a type of persistent lasting seizure with high mortality and morbidity. Numerous medications are suggested for the treatment of SE, two of which are sodium valproate and phenytoin. The purpose of this study is to conduct a comparison between the effi ciencies of intravenous sodium valproate and phenytoin in the treatment of this type of epilepsy. Methods: This is a clinical trial study conducted on SE-suffering patients admitted to the emergency departments of Al-Zahra and Ayatollah Kashani Medical Centers of Isfahan in 2009 and 2010. The patients were randomly assigned into two groups and taken under treatment, separately by intravenous infusion sodium valproate and phenytoin. Results: No significant difference was observed between the two groups (at P = 0.06). In terms of incidence of the clinical complications, the incidence of clinical complications in the two groups was significantly different (at P = 0.03). Conclusions: Based on the findings the efficiency of sodium valproate is larger than that of the phenytoin, and thus, the treatment by sodium valproate is preferred over the treatment by phenytoin.
The Hematology Profiles of Adults Affiliated with Epilepsy after Receiving Valproic Acid Therapy
Open Access Macedonian Journal of Medical Sciences
AIM: Epilepsy is a socially significant neurological disease spread all over the world. Valproic acid (VPA) is one of the most used antiepileptic drug (AED) for treatment which has some side effects on hematology field. A nowadays update to the adult safety information is needed. The current aim is to conduct a cross-sectional study and to describe the hematology profile of adults with epilepsy treated by VPA. MATERIALS AND METHODS: Data collection was done retrospectively and includes characteristics of the subjects such as age, gender, electroencephalography (EEG) finding, duration of VPA treatment, type of treatment, and hematology profile. We report 50 subjects treated by VPA at least 1 year. RESULTS: The mean age is 46, 4 years, 50% male and 50% female. About 92% were generalized tonic-clonic seizure. Seven percent were partial complex epilepsy. Twenty-four EEG results were abnormal (48%). We found 4 cases (7%) of thrombocytopenia at therapeutic dose and 8 cases (16%) of mild...