Efficacy Study of Intravenous Sodium Valproate in Addition to First Line Anti Epileptic Treatment of Generalized Convulsive Status Epilepticus.
Information source: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Generalized Convulsive Status Epilepticus; Intensive Care Unit
Intervention: Intravenous Sodium Valproate (Drug); Placebo (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Assistance Publique - Hôpitaux de Paris Official(s) and/or principal investigator(s): HervĂ© OUTIN, MD, Principal Investigator, Affiliation: Service de RĂ©animation MĂ©dico Chirurgicale, HĂ´pital Poissy Saint-Germain en Laye
Overall contact: Hervé OUTIN, MD, Phone: +33 (1) 39 27 52 65, Email: outin@chi-poissy-st-germain.fr
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Number of patients in ICU for a GCSE discharged alive from the hospital at Day 15.
Secondary outcome: Frequency of refractory status epilepticusMorbidity related to ICU stay Cognitive dysfunction
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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. Generalized convulsive status epilepticus can be
controlled or not at time of inclusion.
- Anti convulsant therapy less than 3 hours.
- 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.
Exclusion Criteria:
- Other type of status epilepticus (including atypical form) occured before the onset
of anti epileptic treatment (However, generalized convulsive status epilepticus
preceded by focal or non convulsive seizures can be included)
- 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
- Previous to inclusion, long-term treatment with sodium valproate, divalproate or
valpromide
- Pre-existing chronic or acute hepatitis
- Liver disease (Transaminase > 3 times standards, Prothrombin rate < 70 % with Factor
V rate < 70 %)
- Family history of acute hepatitis, especially drug-related hepatitis
- Other sodium valproate Contraindications : Hypersensitivity to sodium valproate or
derivatives, hepatic porphyria, mefloquine or hypericum taking
- life expectancy expected ≤ 3 months,
- Patients already already included in another clinical trial on GCSE.
- Non affiliation to a social health care
Locations and Contacts
Hervé OUTIN, MD, Phone: +33 (1) 39 27 52 65, Email: outin@chi-poissy-st-germain.fr
HĂ´pital Raymond Poincare, Garche, Haute de Seine 92380, France; Recruiting BERNARD CLAIRE, MD
Additional Information
Starting date: February 2013
Last updated: June 23, 2015
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