Epilepticus; Status, Focal MotorPhase 3PEPSINCT04309721
Perampanel in Focal Status Epilepticus
A Phase 3 study testing Perampanel in people with Epilepticus; Status, Focal Motor, run by Assistance Publique - Hôpitaux de Paris at 10 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epilepticus; Status, Focal Motor
- What is being tested?
- Perampanel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 10 sitesFrance
- Study dates
- 2 Nov 2022to 13 Nov 2023
- Phase
- Phase 3
- 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
- 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)
- 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.
- Affiliation to a French social security system (recipient or assign) excluding "Aide Médicale" Etat (AME)
Who cannot join
- Known severe liver (Factor V <50 %) or kidney (glomerular filtration rate : 15-29 ml/min/1,72 m2) insufficiency
- Women with known or clinically detected pregnancy
- Patients with known allergies to perampanel or to any of the excipients mentioned in the summary of product characteristics(SmPC)
- Patients with postanoxic status
- Patients in coma (Glasgow<8)
- Patients with motor events for which a nonepileptic psychogenic origin is suspected
Show all 10Show fewer
- Patients whose status epilepticus is linked to a pathological condition, such as trauma, who needed immediate surgery
- Known current treatment by perampanel
- Known galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases)
- Known participation in another trial with medication and/or previously included in PEPSI study
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
Urgences, CHU Lille (Hôpital Roger Salengro)
Lille, 59037
Neuro-physiologie clinique, CHU Lille (Hôpital Roger Salengro)
Lille
Réanimation polyvalente, CHU (Hopital Roger Salengro)
Lille
Department of Neurology, Epilepsy Unit, Pitié-Salpêtrière Hospital
Paris, 75013
Hôpital Pitié Salpêtrière - ICU
Paris, 75013
Réanimation Polyvalente, GH Paris Saint Joseph
Paris, 75014
Neurologie et Neurovasculaire, GH Paris Saint Joseph
Paris
S.A.U, Pitié-Salpêtrière Hospital
Paris
Accueil des Urgences, Centre Hospitalier de Versailles - André Mignot
Versailles
Neurologie, Centre Hospitalier de Versailles - André Mignot
Versailles, Île-de-France Region, 78157
About this study
Official title: Efficacy of add-on PEramPanel in Focal Motor Status Epilepticus
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.
Read the 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.
- Conditions
- Epilepticus; Status, Focal Motor
- Being tested
- Perampanel, Placebo
- Keywords
- Perampanel, Placebo, Antiepileptic drug
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerampanelDrug
Also called Experimental group
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
Also called Control group
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
| Study group | Role | What they receive |
|---|---|---|
| Perampanel | Experimental | immediate enteral administration of Perampanel, 12 mg Receives: Drug: Perampanel |
| Placebo | Placebo comparator | immediate enteral administration of placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Within de 6 hours after the perampanel or placebo administration
Secondary outcomes (16)
Seizure cessation
Seizure cessation is defined clinically by the interruption of any epileptic movements (clonic, tonic or myoclonic)
Measured: at 3 hours and 6 hours after the perampanel or placebo administration
Time to seizure cessation
Measured: within the 6 hours after the administration of perampanel or placebo
The need for endotracheal intubation
Measured: 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
Measured: 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
Measured: 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
Measured: From hour 3 until hour 24 after the administration of perampanel or placebo
Rate of patient with status epilepticus recurrence, in patients with seizure cessation
Status epilepticus recurrence is defined as focal motor seizure lasting 10 minutes or more, or repeated focal motor seizures (≥4 seizures in 10 min), between hour 3 and hour 24 after the administration of perampanel or placebo.
Measured: From hour 3 until hour 24 after the administration of perampanel or placebo
Rate of patients with secondary generalized seizures
Secondary generalized seizures is defined as convulsive tonic or clonic bilateral seizure lasting less than 5 minutes
Measured: From hour 0 until hour 24 after the administration of perampanel or placebo
Progression to a convulsive generalized status epilepticus
Convulsive generalized status epilepticus is defined as convulsive tonic or clonic bilateral seizure lasting more than 5 minutes or more, or 2 or more seizures in 5 minutes without recovery of consciousness between the seizures
Measured: From hour 0 until hour 24 after the administration of perampanel or placebo
Mortality rate at the end of the study period
Measured: Up to 14 days (end of hospitalization) or 14 days if the patient is still hospitalized
Glasgow Outcome Scale score at the end of the study period
Glasgow Outcome Scale (GOS) is 5 values score from 1 (death) to 5 (resumption to normal life; there may be minor neurologic and/or psychological deficits).
Measured: Up to 14 days (end of hospitalization) or 14 days if the patient is still hospitalized
Global neurological state at the end of the study period
The neurological state of patients will be evaluated for comparison with that before status epilepticus. Three states will be distinguished: unchanged, new neurological deficit or death
Measured: Up to 14 days (end of hospitalization) or 14 days if patient is still hospitalized
Number of adverse events and their severity
Measured: from randomization until to 14 days after the administration of perampanel or placebo
Subgroup analysis of the primary and secondary outcomes measure according to the etiology
Several etiological categories will be defined :
- acute symptomatic versus remote symptomatic versus cryptogenic causes
- identification of a brain lesion versus not
Measured: At H0 (below or above the median of SE duration
Subgroup analysis of the primary and secondary outcomes measure according to duration of status epilepticus
Measured: At H0 (below or above the median of SE duration
Subgroup analysis of the primary and secondary outcomes measure according to type of conventional antiepileptic drug administrated
Measured: At H0 (below or above the median of SE duration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start2 Nov 2022
- Primary completion2 Nov 2022
- Study completion13 Nov 2023
Why it stopped: Lack of inclusion
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epilepticus; Status, Focal MotorStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent Navarro, DDS,PhD, Principal investigator, Groupe Hospitalier Pitie-Salpetriere
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04309721
- Sponsor's protocol ID
- P160949J
- Other IDs
- 2019-000882-19, 2019
- Acronym
- PEPSI
- Status last verified
- Dec 2023
- First submitted
- 4 Dec 2019
- Last updated
- 14 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of add-on PEramPanel in Focal Motor Status Epilepticus
- ClinicalTrials.gov ID
- NCT04309721
- Acronym / sponsor ID
- PEPSI / P160949J
- Conditions
- Epilepticus; Status, Focal Motor
- Keywords
- Perampanel, Placebo, Antiepileptic drug
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of inclusion
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 2 Nov 2022 (actual)
- Primary completion
- 2 Nov 2022 (actual)
- Study completion
- 13 Nov 2023 (actual)
- First posted
- 16 Mar 2020 (actual)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Perampanel | Experimental | Drug: Perampanelimmediate enteral administration of Perampanel, 12 mg |
| Placebo | Placebo comparator | Drug: Placeboimmediate enteral administration of placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
- 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.
- Affiliation to a French social security system (recipient or assign) excluding "Aide Médicale" Etat (AME)
Key exclusion criteria (10 listed)
- Known severe liver (Factor V <50 %) or kidney (glomerular filtration rate : 15-29 ml/min/1,72 m2) insufficiency
- Women with known or clinically detected pregnancy
- Patients with known allergies to perampanel or to any of the excipients mentioned in the summary of product characteristics(SmPC)
- Patients with postanoxic status
- Patients in coma (Glasgow<8)
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 |
|---|---|---|
| PerampanelAlso: Experimental groupSingle-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 | Drug | Perampanel |
| PlaceboAlso: Control groupSingle-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 | Drug | Placebo |
Primary outcome
Administration or not of either (i) an additional second-line antiepileptic drug, either intravenous or orally, or (ii) a third-line (anesthetic drug)
Time frame: Within de 6 hours after the perampanel or placebo administration
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
16 secondary outcomes
Seizure cessation
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
Time frame: at 3 hours and 6 hours after the perampanel or placebo administration
Duration of hospitalization
Time frame: From randomization untill 14 days after the administration of perampanel or placebo
Rate of patient with seizure recurrence
Time frame: From hour 3 until hour 24 after the administration of perampanel or placebo
Rate of patient with status epilepticus recurrence, in patients with seizure cessation
Time frame: From hour 3 until hour 24 after the administration of perampanel or placebo
Rate of patients with secondary generalized seizures
Time frame: From hour 0 until hour 24 after the administration of perampanel or placebo
Progression to a convulsive generalized status epilepticus
Time frame: From hour 0 until hour 24 after the administration of perampanel or placebo
Mortality rate at the end of the study period
Time frame: Up to 14 days (end of hospitalization) or 14 days if the patient is still hospitalized
Glasgow Outcome Scale score at the end of the study period
Time frame: Up to 14 days (end of hospitalization) or 14 days if the patient is still hospitalized
Global neurological state at the end of the study period
Time frame: Up to 14 days (end of hospitalization) or 14 days if patient is still hospitalized
Number of adverse events and their severity
Time frame: from randomization until to 14 days after the administration of perampanel or placebo
Subgroup analysis of the primary and secondary outcomes measure according to the etiology
Time frame: At H0 (below or above the median of SE duration
Subgroup analysis of the primary and secondary outcomes measure according to duration of status epilepticus
Time frame: At H0 (below or above the median of SE duration
Subgroup analysis of the primary and secondary outcomes measure according to type of conventional antiepileptic drug administrated
Time frame: At H0 (below or above the median of SE duration)
Results and safety
The study was stopped early (reason given: Lack of inclusion). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2023.
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.
Vincent Navarro, DDS,PhD principal investigator
Groupe Hospitalier Pitie-Salpetriere
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Perampanel in people with Epilepticus; Status, Focal Motor, run by Assistance Publique - Hôpitaux de Paris at 10 sites 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 3 inclusion and 10 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: stopped early, as of the sponsor's last update on 14 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of inclusion). Results are not available in the source record.
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?
Administration or not of either (i) an additional second-line antiepileptic drug, either intravenous or orally, or (ii) a third-line (anesthetic drug) (time frame: Within de 6 hours after the perampanel or placebo administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Dec 2023.