Perampanel in Focal Status Epilepticus (PEPSI)

Assistance Publique - Hôpitaux de Paris

Status and phase: Terminated; Phase 3

Conditions: Epilepticus; Status, Focal Motor

Treatments: Drug: Placebo; Drug: Perampanel

Study type: Interventional

Funder types: Other

Identifiers

NCT04309721

2019-000882-19 (EudraCT Number)

P160949J

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1 patient

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1 participants in 2 patient groups, including a placebo group

Perampanel

Experimental group

Description:

immediate enteral administration of Perampanel, 12 mg

Treatment:

Drug: Perampanel

Placebo

Placebo Comparator group

Description:

immediate enteral administration of placebo

Treatment:

Drug: Placebo