Evidence map›Paper›PMID 36624526›Full record

Trial reportCritical care (London, England)2023

Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial.

Tarek Sharshar, Raphaël Porcher, Pierre Asfar, Lamiae Grimaldi, Julien Jabot, Laurent Argaud, Christine Lebert, Pierre-Edouard Bollaert, Marie Line Harlay, Patrick Chillet and 12 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Critical care (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01791868 (Randomized and Multicenter Study Assessing the Efficacy of Intravenous Sodium Valproate in Addition to First Line Anti Epileptic Treatment of Generalized Convulsive Status Epilepticus.), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01791868 nacompletednot on this map

Randomized and Multicenter Study Assessing the Efficacy of Intravenous Sodium Valproate in Addition to First Line Anti Epileptic Treatment of Generalized Convulsive Status Epilepticus.

TypeinterventionalSponsorAssistance Publique - Hôpitaux de ParisRan2013 to 2018Enrolled245ConditionsGeneralized Convulsive Status Epilepticus, Intensive Care UnitArmsIntravenous Sodium Valproate, Placebo
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
  3. Advancements in Valproate Therapy for Seizures, Migraines, and Bipolar Disorders.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 20 institutions in 4 countries.

Tarek SharsharNeuro-Intensive Care Medicine, Anaesthesiology and ICU Department, GHU-Psychiatry and Neurosciences, Pole Neuro, Sainte-Anne Hospital, Institute of Psychiatry and Neurosciences of Paris, INSERM U1266, Université Paris Cité, Paris, France. t.sharshar@ghu-paris.fr.
Raphaël PorcherUniversité Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS), F-75004, Paris, France.
Pierre AsfarDepartment of Medical Intensive Care, University Hospital, Angers, France.
Lamiae GrimaldiClinical Research Unit, Assistance Publique - Hôpitaux de Paris University Paris-Saclay. Faculty of medicine, University of Versailles Saint-Quentin en Yvelines. Inserm U1018 Team Anti-infective evasion and pharmacoepidemiology, Boulogne-Billancourt, France.
Julien JabotMedical-Surgical Intensive Care Unit, CHU Felix-Guyon, Saint-Denis, La Réunion, France.
Laurent ArgaudService de Médecine Intensive-Réanimation, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France.
Christine LebertMédecine Intensive Réanimation, Centre Hospitalier Départemental de Vendée, La Roche-sur-Yon, France.
Pierre-Edouard BollaertCHRU-Nancy, Service de Médecine Intensive Réanimation, Université de Lorraine, 54000, Nancy, France.
Marie Line HarlayMédecine Intensive Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Patrick ChilletService de Médecine Intensive - Réanimation, Centre hospitalier Léon Bourgeois, Châlons en Champagne, France.
Eric MauryService de Médecine Intensive et Réanimation Hôpital Saint-Antoine, Paris-Sorbonne Université, Paris, France.
Francois SantoliMédecine Intensive-Réanimation, Centre Hospitalier Robert Ballanger, Aulnay sous Bois, France.
Pascal BlancRéanimation Médico Chirurgicale, Centre Hospitalier René Dubos, Pontoise, France.
Romain SonnevilleUniversité de Paris Cité, INSERM UMR1137, Paris, France.
Dinh Chuyen VuGeneral Intensive Care Unit, Sud-Essonne Hospital, Etampes, France.
Benjamin RohautDepartment of Neurology, Neuro-ICU & Brain institute - ICM, Pitié-Salpêtrière Hospital APHP, Sorbonne Université, Paris, France.
Aurelien MazeraudAnaesthesiology and ICU Department, GHU-Psychiatry and Neurosciences, Pole Neuro, Sainte-Anne Hospital, Perception and Memory Unit, Neurosciences Department, Institut Pasteur, Université Paris Cité, Paris, France.
Jean-Claude AlvarezDepartment of Pharmacology and Toxicology, Inserm U-1173, Raymond Poincare Hospital, AP-HP, Versailles Saint-Quentin-en-Yvelines University, Paris-Saclay University, 104 Boulevard Raymond Poincare, 92380, Garches, France.
Vincent NavarroAP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, Sorbonne Université, and Paris Brain Institute, Paris, France.
Bernard ClairGeneral Intensive Care Unit, APHP, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France.
Hervé OutinIntensive Care Unit Centre Hospitalier Intercommunal, Poissy/Saint-Germain-en-Laye, France.
Valse investigators and for the Groupe d’Explorations Neurologiques en Reanimation (GENER)
Inserm · FRSorbonne Université · FRAllen Institute for Brain Science · USCentre hospitalier Robert-Ballanger · FRCentre Hospitalier Départemental Vendée · FRCentre Hospitalier Intercommunal de Poissy · FRCentre Hospitalier Universitaire de La Réunion · FRHôpitaux Universitaires de Strasbourg · FRCentre Hospitalier Régional et Universitaire de Nancy · FRCentre Hospitalier René-Dubos · FRCentre Hospitalier Sainte-Anne · FRConseil Régional de Champagne-Ardenne · FRUniversité Claude Bernard Lyon 1 · FRUniversité de Versailles Saint-Quentin-en-Yvelines · FRUniversité Paris Cité · FRAssistance Publique – Hôpitaux de Paris · FRCentre Hospitalier Sud-Essonne Dourdan-Etampes · FRCentre Hospitalier Universitaire d'Angers · FRHôpital Edouard Herriot · FRHôpital Raymond-Poincaré · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGeneralised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE.

methodsThis was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90.

resultsA total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes.

conclusionsVPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. TRIAL REGISTRATION NO: NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Indexed as

BenzodiazepinesValproic AcidAdministration, IntravenousAdultHospitalizationHumansPatient DischargeBenzodiazepinesValproic AcidGeneralised convulsive status epilepticusIntensive care unitSeizureValproic acid

Identifiers

PMID36624526
PMCPMC9830759
OpenAlexW4313829210

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.