Clinical trial NCT04309721: Perampanel in Focal Status Epilepticus
Official title: Efficacy of add-on PEramPanel in Focal Motor Status Epilepticus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Epilepticus; Status, Focal Motor
Keywords: Perampanel
Placebo
Antiepileptic drug
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-03-16
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized controlled trial on focal motor status epilepticus (SE), studying the add-on efficacy of the enteral administration of perampanel (PER) to a conventional intravenous antiepileptic drug.

Detailed description: In spite of the use of various antiepileptic drugs, the SE, generalized or focal, are refractory to the treatment in around 25 % of the cases. There is therefore a need to develop new therapy with novel synaptic targets.

New antiepileptic drugs emerge as potential drugs for SE. Perampanel (PER) is a new drug available for add-on therapy in patients with a focal epilepsy. The mechanism of action of this drug is original, as it is a non-competitive α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist. Several studies suggested that AMPA-mediated glutamatergic transmission plays an important rule during the SE.

In this study the investigator will focus on patients suffering from early focal motor SE, for several reasons:

(i) There is no randomized controlled double-blind trial in this population, and therefore no evidence to help physicians.

(ii) The investigator aims to perform a trial on early SE, after failure of only one drug (a benzodiazepine, recommended as first line treatment), in order to properly evaluate the effect of the tested drug (add-on of perampanel).

(iii) The perampanel is available only for oral administration. Focal SE usually does not affect the vital prognosis and can be treated less aggressively. Use of oral loading doses of antiepileptic drugs is frequent, and therapies may be changed or adapted in the time-frame of hours or days.

(iv) Patients with a focal SE, presenting motor symptoms, can be included without the need of an EEG. Similarly, the primary end-point, cessation of the motor events, does not require specific exam, and can also be done clinically.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18 years or above, including the protected adults with a focal motor status epilepticus, defined by prominent clinically objective focal motor symptoms (clonic, tonic, myoclonic, adversive or oculoclonic), lasting for more than 10 minutes before any treatment or repeated focal motor seizures during this period (≥ 4 seizures in 10 min)
2. The focal motor status continues (or patients show ≥ 2 focal motor seizures) 5 minutes or more after the beginning of administration of benzodiazepines. The delay between administration of benzodiazepines and randomization must not exceed 6 hours.
3. Affiliation to a French social security system (recipient or assign) excluding "Aide Médicale" Etat (AME)

Exclusion Criteria:

1. Known severe liver (Factor V \<50 %) or kidney (glomerular filtration rate : 15-29 ml/min/1,72 m2) insufficiency
2. Women with known or clinically detected pregnancy
3. Patients with known allergies to perampanel or to any of the excipients mentioned in the summary of product characteristics(SmPC)
4. Patients with postanoxic status
5. Patients in coma (Glasgow\<8)
6. Patients with motor events for which a nonepileptic psychogenic origin is suspected
7. Patients whose status epilepticus is linked to a pathological condition, such as trauma, who needed immediate surgery
8. Known current treatment by perampanel
9. Known galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases)
10. Known participation in another trial with medication and/or previously included in PEPSI study

Primary outcomes:
measure: Administration or not of either (i) an additional second-line antiepileptic drug, either intravenous or orally, or (ii) a third-line (anesthetic drug)
timeFrame: Within de 6 hours after the perampanel or placebo administration
Secondary outcomes:
measure: Seizure cessation
timeFrame: at 3 hours and 6 hours after the perampanel or placebo administration
measure: Time to seizure cessation
timeFrame: within the 6 hours after the administration of perampanel or placebo
measure: The need for endotracheal intubation
timeFrame: within the 24 hours after the administration of perampanel or placebo
measure: Percentage of patients with altered consciousness
timeFrame: at 3 hours and 6 hours after the perampanel or placebo administration
measure: Duration of hospitalization
timeFrame: From randomization untill 14 days after the administration of perampanel or placebo
measure: Rate of patient with seizure recurrence
timeFrame: From hour 3 until hour 24 after the administration of perampanel or placebo
measure: Rate of patient with status epilepticus recurrence, in patients with seizure cessation
timeFrame: From hour 3 until hour 24 after the administration of perampanel or placebo
measure: Rate of patients with secondary generalized seizures
timeFrame: From hour 0 until hour 24 after the administration of perampanel or placebo
measure: Progression to a convulsive generalized status epilepticus
timeFrame: From hour 0 until hour 24 after the administration of perampanel or placebo
measure: Mortality rate at the end of the study period
timeFrame: Up to 14 days (end of hospitalization) or 14 days if the patient is still hospitalized
measure: Glasgow Outcome Scale score at the end of the study period
timeFrame: Up to 14 days (end of hospitalization) or 14 days if the patient is still hospitalized
measure: Global neurological state at the end of the study period
timeFrame: Up to 14 days (end of hospitalization) or 14 days if patient is still hospitalized
measure: Number of adverse events and their severity
timeFrame: from randomization until to 14 days after the administration of perampanel or placebo
measure: Subgroup analysis of the primary and secondary outcomes measure according to the etiology
timeFrame: At H0 (below or above the median of SE duration
measure: Subgroup analysis of the primary and secondary outcomes measure according to duration of status epilepticus
timeFrame: At H0 (below or above the median of SE duration
measure: Subgroup analysis of the primary and secondary outcomes measure according to type of conventional antiepileptic drug administrated
timeFrame: At H0 (below or above the median of SE duration)
Other outcomes:
Locations:
city: Versailles
country: France
facility: Neurologie, Centre Hospitalier de Versailles - André Mignot
state: Ile De France
city: Lille
country: France
facility: Urgences, CHU Lille (Hôpital Roger Salengro)
city: Lille
country: France
facility: Neuro-physiologie clinique, CHU Lille (Hôpital Roger Salengro)
city: Lille
country: France
facility: Réanimation polyvalente, CHU (Hopital Roger Salengro)
city: Paris
country: France
facility: Department of Neurology, Epilepsy Unit, Pitié-Salpêtrière Hospital
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière - ICU
city: Paris
country: France
facility: Réanimation Polyvalente, GH Paris Saint Joseph
city: Paris
country: France
facility: Neurologie et Neurovasculaire, GH Paris Saint Joseph
city: Paris
country: France
facility: S.A.U, Pitié-Salpêtrière Hospital
city: Versailles
country: France
facility: Accueil des Urgences, Centre Hospitalier de Versailles - André Mignot
Study officials:
affiliation: Groupe Hospitalier Pitié-Salpêtrière
name: Vincent Navarro, DDS,PhD
role: PRINCIPAL_INVESTIGATOR
References: