Efficacy Study of Intravenous Sodium Valproate in Addition to First Line Anti Epileptic Treatment of Generalized Convulsive Status Epilepticus.

NCT01791868 | Completed DMC

• 2 other identifiers: P1001482011-006340-75
• Study Type: interventional
• Target: 245
• Locations: 1 country
• Sites: 1

Brief Summary

Study Hypothesis Generalized Convulsive Status Epilepticus (GCSE) is a medical emergency associated with an increased morbidity and a prolonged length of hospital stay. Only 50% of patients are discharged from the hospital within the first month after GCSE. Recent Guidelines from Experts highlight the necessity to improve the efficiency of the first line anti-epileptic (AE) therapy. Intravenous Sodium Valproate (SV) might be an adjuvant AE drug to the recommended first line AEs. Intravenous SV is available, well tolerated and easily injectible but also has pharmacologic properties for reducing the risk of seizures relapses and for being neuroprotective. However, efficacy of intravenous as an adjuvant therapy in GCSE has never been properly assessed. Primary Purpose The primary purpose is to assess if the association of intravenous Sodium Valproate with the recommended treatment for Generalized Convulsive Status Epilepticus increases to 20 % the number of living patients, discharged from the hospital at day 15.

Conditions

Generalized Convulsive Status Epilepticus; Intensive Care Unit

Keywords

Generalized convulsive status epilepticus; Sodium valproate; Refractory status epilepticus; Mortality; Epilepsy; Intensive Care Unit; Neurological sequela; Quality of life; Adult

Outcome Measures

Primary Outcomes (1)

• Number of patients in ICU for a GCSE discharged alive from the hospital at Day 15.

  Increasing by 20 % the number of patients admitted in ICU for a GCSE who will be discharged alive from the hospital at Day 15.

  15 days

Secondary Outcomes (3)

• Frequency of refractory status epilepticus

  3 months

• Morbidity related to ICU stay

  3 months

• Cognitive dysfunction

  3 months

Study Arms (2)

Intravenous sodium valproate

EXPERIMENTAL

Intravenous sodium valproate: 30 mg/kg during 15 min then 1 mg/kg/h during 12 h

Drug: Intravenous Sodium Valproate

Intravenous Placebo

PLACEBO COMPARATOR

Intravenous Placebo: NaCl 0,9 % during 15 min at first then during 12 h.

Drug: Placebo

Interventions

Intravenous Sodium Valproate DRUG

According to randomization arm, patients will be treated either by intravenous sodium valproate (30 mg/kg during 15 min then 1 mg/kg/h during 12 h) or intravenous placebo. All included patients will benefit from first-line anti epileptic drugs and symptomatic medical care, in agreement with the French Experts Recommendation 2009(RFE 2009).

Also known as: DEPAKINE®

Intravenous sodium valproate

Placebo DRUG

According to randomization arm, patients will be treated either by intravenous sodium valproate (30 mg/kg during 15 min then 1 mg/kg/h during 12 h) or intravenous placebo. All included patients will benefit from first-line anti epileptic drugs and symptomatic medical care, in agreement with the French Experts Recommendation 2009(RFE 2009).

Also known as: NaCl 0.9%

Intravenous Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient older than 18.
• Admitted in a participating ICU for generalized convulsive status epilepticus (GCSE) i.e. with persistent or repeated generalized seizures without regaining consciousness over a period of five minutes. provided that the duration of the treatment prior antiepileptic does not exceed:
• Twenty-four hours if GCSE persisted or is recurrent.

You may not qualify if:

• Other type of status epilepticus (including atypical form) occured before the onset of anti epileptic.
• Female patient of childbearing age ≥ 18 ans et \< 50 ans
• Patient prior treated by depakine in emergency for the GCSE
• The length of stay in hospital expected before the occurrence of GCSE \> 15 days.
• Expected Length of stay in ICU \<12h .
• Hypoxic-ischemic encephalopathy.
• Pregnant women, eclampsia checked by a systematic pregnancy test.
• Pre-existing chronic or acute hepatitis, or Cirrhosis B or C.
• Family history of acute hepatitis, especially drug-related hepatitis
• Other sodium valproate Contraindications : Hypersensitivity to sodium valproate or derivatives, acute or chronic hepatitis; personal or family history of severe hepatitis, in particular drug; hepatic porphyria, mefloquine or hypericum taking.
• life expectancy expected ≤ 3 months.
• Patients already included in another clinical trial on GCSE.
• Non affiliation to a social health care.
• Patients under tutelage.
• Patient has already been included in this protocol and who completed the clinical trial.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Raymond Poincare

Garche, Haute de Seine, 92380, France

Location

Related Publications (2)

• Sharshar T, Porcher R, Asfar P, Grimaldi L, Jabot J, Argaud L, Lebert C, Bollaert PE, Harlay ML, Chillet P, Maury E, Santoli F, Blanc P, Sonneville R, Vu DC, Rohaut B, Mazeraud A, Alvarez JC, Navarro V, Clair B, Outin H; Valse investigators and for the Groupe d'Explorations Neurologiques en Reanimation (GENER). Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial. Crit Care. 2023 Jan 9;27(1):8. doi: 10.1186/s13054-022-04292-7.

  PMID: 36624526 DERIVED

• Sharshar T, Ben Hadj Salem O, Porcher R, Grimaldi-Bensouda L, Heming N, Clair B, Azabou E, Mazeraud A, Rohaut B, Outin H. Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus in Adults Admitted to Intensive Care Units: Protocol for a Double-Blind, Multicenter Randomized Controlled Trial. JMIR Res Protoc. 2021 Feb 24;10(2):e22511. doi: 10.2196/22511.

  PMID: 33625371 DERIVED

MeSH Terms

Conditions

Status Epilepticus; Epilepsy

Interventions

Valproic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Hervé OUTIN, MD

  Service de Réanimation Médico Chirurgicale, Hôpital Poissy Saint-Germain en Laye

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2013
• First Posted: February 15, 2013
• Study Start: February 1, 2013
• Primary Completion: July 1, 2018
• Study Completion: October 1, 2018
• Last Updated: October 16, 2018

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)