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

Primary Purpose

Generalized Convulsive Status Epilepticus, Intensive Care Unit

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Intravenous Sodium Valproate
Placebo
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Generalized Convulsive Status Epilepticus focused on measuring Generalized convulsive status epilepticus, Sodium valproate, Refractory status epilepticus, Mortality, Epilepsy, Intensive Care Unit, Neurological sequela, Quality of life, Adult

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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:

    • Six hours if GCSE is already controlled at the time of inclusion (= disappearance seizures regardless of the state of consciousness)
    • Twenty-four hours if GCSE persisted or is recurrent.
  • Written informed consent collected from close relation or a family member of the patient. Otherwise, inclusion according to French Health Code in case of medical emergency. In this case, the written informed consent of patient has to be collected as soon as possible then. in absence of a close of patient, the patient may be still included. the consent of the prosecution will be collected

Exclusion Criteria:

  • 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.

Sites / Locations

  • Hôpital Raymond Poincare

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intravenous sodium valproate

Intravenous Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Frequency of refractory status epilepticus
To determine if intravenous SV as an adjuvant anti-epileptic drug, and irrespectively of the cause of GCSE, decreases as frequency of refractory status epilepticus at 3 months without increase in rate of side effects.
Morbidity related to ICU stay
To determine if intravenous SV as an adjuvant anti-epileptic drug, and irrespectively of the cause of GCSE, decreases as morbidity related to ICU stay at 3 months without increase in rate of side effects.
Cognitive dysfunction
To determine if intravenous SV as an adjuvant anti-epileptic drug, and irrespectively of the cause of GCSE, decreases as cognitive dysfunction at 3 months without increase in rate of side effects.

Full Information

First Posted
February 13, 2013
Last Updated
October 15, 2018
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT01791868
Brief Title
Efficacy Study of Intravenous Sodium Valproate in Addition to First Line Anti Epileptic Treatment of Generalized Convulsive Status Epilepticus.
Acronym
VALSE
Official Title
Randomized and Multicenter Study Assessing the Efficacy of Intravenous Sodium Valproate in Addition to First Line Anti Epileptic Treatment of Generalized Convulsive Status Epilepticus.
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
February 2013 (Actual)
Primary Completion Date
July 2018 (Actual)
Study Completion Date
October 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
Patient admitted Intensive Care Unit (ICU) for a Generalized Convulsive Status Epilepticus (GCSE) will be randomized if they fulfil the inclusion criteria and after the written informed consent is obtained from the patient's next of kin. In clack of closed relatives, patients could be included according to the French Health Code for Case of medical emergency. In this situation, patient's consent should be then obtained as soon as possible 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 Experts recommendation (RFE 2009). From day-1 to day-15, level consciousness(Glasgow Coma Scale, Richmond Agitation Sedation Scale), delirium (Confusion Assessment Method For Intensive Care Unit), reoccurrence of seizure, vital signs, organ dysfunction (Simplified Acute Physiology Score II, Sequential Organ Failure) will be daily assessed. At day 2, the preventive oral anti-epileptic drug will be prescribed by a neurologist, blinded from randomization. At Day 15 and Day 30, neurological status, cognitive functions (Mini Mental State Examination, Frontal Assessment Battery, Glasgow Outcome Scale), and quality of life (SF36) will be assessed by a neurologist, also not aware of the randomization. The number of patients alive and discharged from Hospital day 15 15th day will assessed. 300 patients with GCSE will be randomized, 150 in each arm, in 16 ICUs and over a period of 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
245 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intravenous sodium valproate
Arm Type
Experimental
Arm Description
Intravenous sodium valproate: 30 mg/kg during 15 min then 1 mg/kg/h during 12 h
Arm Title
Intravenous Placebo
Arm Type
Placebo Comparator
Arm Description
Intravenous Placebo: NaCl 0,9 % during 15 min at first then during 12 h.
Intervention Type
Drug
Intervention Name(s)
Intravenous Sodium Valproate
Other Intervention Name(s)
DEPAKINE®
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
NaCl 0.9%
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number of patients in ICU for a GCSE discharged alive from the hospital at Day 15.
Description
Increasing by 20 % the number of patients admitted in ICU for a GCSE who will be discharged alive from the hospital at Day 15.
Time Frame
15 days
Secondary Outcome Measure Information:
Title
Frequency of refractory status epilepticus
Description
To determine if intravenous SV as an adjuvant anti-epileptic drug, and irrespectively of the cause of GCSE, decreases as frequency of refractory status epilepticus at 3 months without increase in rate of side effects.
Time Frame
3 months
Title
Morbidity related to ICU stay
Description
To determine if intravenous SV as an adjuvant anti-epileptic drug, and irrespectively of the cause of GCSE, decreases as morbidity related to ICU stay at 3 months without increase in rate of side effects.
Time Frame
3 months
Title
Cognitive dysfunction
Description
To determine if intravenous SV as an adjuvant anti-epileptic drug, and irrespectively of the cause of GCSE, decreases as cognitive dysfunction at 3 months without increase in rate of side effects.
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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: Six hours if GCSE is already controlled at the time of inclusion (= disappearance seizures regardless of the state of consciousness) Twenty-four hours if GCSE persisted or is recurrent. Written informed consent collected from close relation or a family member of the patient. Otherwise, inclusion according to French Health Code in case of medical emergency. In this case, the written informed consent of patient has to be collected as soon as possible then. in absence of a close of patient, the patient may be still included. the consent of the prosecution will be collected Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hervé OUTIN, MD
Organizational Affiliation
Service de Réanimation Médico Chirurgicale, Hôpital Poissy Saint-Germain en Laye
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Raymond Poincare
City
Garche
State/Province
Haute DE Seine
ZIP/Postal Code
92380
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
33625371
Citation
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.
Results Reference
derived

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

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