Perampanel in Focal Status Epilepticus

Phase 3TerminatedNCT04309721

Assistance Publique - Hôpitaux de Paris1 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Epilepticus; Status, Focal Motor

Interventions

PerampanelDRUG

Single-dose of Perampanel 12 mg film-coated tablet, will be given orally in patients with status epilepticus that do not involve the oral and pharyngeal musculatures. In alternative, perampanel will be administered by a nasogastric feeding tube, a procedure which has been recently reported to be safe and tolerated in patients with generalised status epilepticus

PlaceboDRUG

Single-dose of placebo of Perampanel, administered orally. Placebo of perampanel will be given orally, in patients with status epilepticus that do not involve the oral and pharyngeal musculatures. In alternative, Placebo of perampanel will be administered by a nasogastric feeding tube, a procedure which has been recently reported to be safe and tolerated in patients with generalised status epilepticus

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (10)

Urgences, CHU Lille (Hôpital Roger Salengro)

Lille, France

Neuro-physiologie clinique, CHU Lille (Hôpital Roger Salengro)

Lille, France

Réanimation polyvalente, CHU (Hopital Roger Salengro)

Lille, France

Outcomes

Primary Outcomes

Administration or not of either (i) an additional second-line antiepileptic drug, either intravenous or orally, or (ii) a third-line (anesthetic drug)

Administration or not of either (i) an additional second-line antiepileptic drug, either intravenous or orally, or (ii) a third-line (anesthetic drug), within the 6 hours following study drug (perampanel or placebo) administration

Time frame: Within de 6 hours after the perampanel or placebo administration

Secondary Outcomes

Seizure cessation

Seizure cessation is defined clinically by the interruption of any epileptic movements (clonic, tonic or myoclonic)

Time frame: at 3 hours and 6 hours after the perampanel or placebo administration

Time to seizure cessation

Time frame: within the 6 hours after the administration of perampanel or placebo

The need for endotracheal intubation

Time frame: within the 24 hours after the administration of perampanel or placebo

Percentage of patients with altered consciousness

Altered consciousness is defined as Glascow Coma Scale (GCS) \<8

Time frame: at 3 hours and 6 hours after the perampanel or placebo administration

Duration of hospitalization

Duration of overall hospitalization (ICU/step down/standard hospitalisation) and duration of hospitalization in ICU/step down unit, both censored 14 days after randomisation

Time frame: From randomization untill 14 days after the administration of perampanel or placebo

Rate of patient with seizure recurrence

Seizure recurrence is defined as focal motor seizure lasting less than 10 minutes, between hour 3 and hour 24 after the administration of perampanel or placeb. Recurrence is defined by reappearance of epileptic movements after a period of at least one hour of seizure cessation

Data from ClinicalTrials.gov

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