Generalized Convulsive Status EpilepticusVALSENCT01791868
Efficacy Study of Intravenous Sodium Valproate in Addition to First Line Anti Epileptic Treatment of Generalized Convulsive Status Epilepticus.
A study testing Intravenous Sodium Valproate in people with Generalized Convulsive Status Epilepticus and Intensive Care Unit, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Generalized Convulsive Status Epilepticus, Intensive Care Unit
- What is being tested?
- Intravenous Sodium Valproate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 245 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2013to Oct 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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 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.
Read the 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.
- Being tested
- Intravenous Sodium Valproate, Placebo
- Keywords
- Generalized convulsive status epilepticus, Sodium valproate, Refractory status epilepticus, Mortality, Epilepsy, Intensive Care Unit, Neurological sequela, Quality of life, Adult
- Medical subject headings
- Status Epilepticus, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous Sodium ValproateDrug
Also called DEPAKINE®
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).
PlaceboDrug
Also called NaCl 0.9%
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).
| Study group | Role | What they receive |
|---|---|---|
| Intravenous sodium valproate | Experimental | Intravenous sodium valproate:
30 mg/kg during 15 min then 1 mg/kg/h during 12 h Receives: Drug: Intravenous Sodium Valproate |
| Intravenous Placebo | Placebo comparator | Intravenous Placebo:
NaCl 0,9 % during 15 min at first then during 12 h. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 15 days
Secondary outcomes (3)
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.
Measured: 3 months
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.
Measured: 3 months
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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionJul 2018
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Generalized Convulsive Status EpilepticusStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 245 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hervé OUTIN, MD, Principal investigator, Service de Réanimation Médico Chirurgicale, Hôpital Poissy Saint-Germain en Laye
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01791868
- Sponsor's protocol ID
- P100148
- Other IDs
- 2011-006340-75
- Acronym
- VALSE
- Status last verified
- Nov 2017
- First submitted
- 13 Feb 2013
- Last updated
- 16 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
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.
PubMed 36624526Sharshar 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.
PubMed 33625371
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01791868
- Acronym / sponsor ID
- VALSE / P100148
- Keywords
- Generalized convulsive status epilepticus, Sodium valproate, Refractory status epilepticus, Mortality, Epilepsy, Intensive Care Unit, Neurological sequela, Quality of life
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 245 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Feb 2013 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 15 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous sodium valproate | Experimental | Drug: Intravenous Sodium ValproateIntravenous sodium valproate: 30 mg/kg during 15 min then 1 mg/kg/h during 12 h |
| Intravenous Placebo | Placebo comparator | Drug: PlaceboIntravenous Placebo: NaCl 0,9 % during 15 min at first then during 12 h. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
- 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
Key exclusion criteria (15 listed)
- 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 .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous Sodium ValproateAlso: DEPAKINE®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). | Drug | Intravenous sodium valproate |
| PlaceboAlso: NaCl 0.9%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). | Drug | Intravenous Placebo |
Primary outcome
Number of patients in ICU for a GCSE discharged alive from the hospital at Day 15.
Time frame: 15 days
Increasing by 20 % the number of patients admitted in ICU for a GCSE who will be discharged alive from the hospital at Day 15.
3 secondary outcomes
Frequency of refractory status epilepticus
Time frame: 3 months
Morbidity related to ICU stay
Time frame: 3 months
Cognitive dysfunction
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Derived from this study: PubMed 36624526Sharshar 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.
- Derived from this study: PubMed 33625371Sharshar 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hervé OUTIN, MD principal investigator
Service de Réanimation Médico Chirurgicale, Hôpital Poissy Saint-Germain en Laye
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intravenous Sodium Valproate in people with Generalized Convulsive Status Epilepticus and Intensive Care Unit, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients in ICU for a GCSE discharged alive from the hospital at Day 15. (time frame: 15 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01791868, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2018.