Comparison Between Lorazepam, Clonazepam and Clonazepam + Fosphenytoin for the Treatment of Out-of-hospital Generalized Status Epilepticus

NCT01870024 | Completed Phase 3

• 2 other identifiers: P1101232012-003795-39
• Study Type: interventional
• Target: 434
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to know on one hand if lorazepam is more (effective) than clonazepam and on the other hand if lorazepam is also effective as the association clonazepam + fosphenytoin in out-of-hospital treatment of the generalized convulsive status epilepticus in adult patients.

Conditions

Status Epilepticus; Epilepsy

Keywords

status epilepticus; epilepsy; seizures; convulsive seizures; convulsions; benzodiazepines; anticonvulsants

Outcome Measures

Primary Outcomes (1)

• Percentage of patient with a cessation of seizures and absence of recurrence

  Percentage of patient with a cessation of seizures and absence of recurrence from 20 minutes until 60 minutes after the beginning of the treatment

  between 20 and 60 minutes after the beginning of the treatment

Secondary Outcomes (11)

• Duration between the first cessation and the recurrence of seizures

  up to 60 minutes

• Percentage of patients having had a second injection of benzodiazepine

  up to 60 minutes

• Percentage of patients having had an injection of the second line treatment

  up to 60 minutes

• Percentage of patients having a general anesthesia for refractory status epilepticus

  up to 60 minutes

• Percentage of patients having had a side effect

  up to 60 minutes

Study Arms (3)

1: Lorazepam + Placebo

ACTIVE COMPARATOR

\[ L + P \] = lorazepam 0,1mg/kg by intravenous injection over a period of 2 to 3 minutes) + placebo 20 mg/kg by intravenous infusion over a period of 15 minutes

Drug: Placebo; Drug: Lorazepam

2: Clonazepam + Placebo

ACTIVE COMPARATOR

\[ C + P \] = clonazepam 0,015 mg/kg by intravenous injection over a period of 2 to 3 minutes + placebo 20 mg/kg by intravenous infusion over a period of 2 15 minutes

Drug: Clonazepam; Drug: Placebo

3: Clonazepam + Fosphenytoin

ACTIVE COMPARATOR

\[ C + F \] = clonazepam 0,015 mg/kg by intravenous injection over a period of 2 to 3 minutes + fosphenytoin 20 mg/kg Equivalent Phenytoin (EP) by intravenous infusion over a period of 15 minutes

Drug: Clonazepam; Drug: Fosphenytoin

Interventions

Clonazepam DRUG

clonazepam 0,015 mg/kg

2: Clonazepam + Placebo; 3: Clonazepam + Fosphenytoin

Fosphenytoin DRUG

fosphenytoin 20 mg/kg Equivalent Phenytoin (EP) by intravenous infusion over a period of 15 minutes

3: Clonazepam + Fosphenytoin

Placebo DRUG

placebo 20 mg/kg by intravenous infusion over a period of 15 minutes

1: Lorazepam + Placebo; 2: Clonazepam + Placebo

Lorazepam DRUG

lorazepam 0,1mg/kg by intravenous injection over a period of 2 to 3 minutes)

1: Lorazepam + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 years or older
• Out-of-hospital management
• presenting one of the criteria below noticed by the physician of the mobile intensive care unit:
• convulsive seizures at the time of treatment and were reported by reliable witnesses to have been continuously convulsing for longer than 5 minutes, without regaining consciousness, or
• if they were having more than 2 repeated convulsive seizures at the time of treatment without regaining consciousness

You may not qualify if:

• Patient having been already included in the study during a previous episode of status epilepticus
• Patient having already received before the arrival of the mobile intensive care unit one of theses studied drugs (lorazepam, clonazepam or fosphenytoin or phenytoin)
• Latent status epilepticus in deep coma
• Cerebral anoxia (post cardio respiratory arrest)
• Severe head trauma
• Patient presenting convulsive seizures of psychogenic origin
• Lennox Gastaut's syndrome
• Decision of urgent intubation
• Patients of more than 110 kg ( estimated weight
• Heart rate \< 60 bpm or \> 150 bpm
• Systolic Blood Pressure \< 90 mmHg
• Atrioventricular block of 2nd or 3rd degree
• Ventricular tachycardia or ventricular fibrillation
• Sensibility known about benzodiazepines, fosphenytoin, phenytoin, other hydantoins, or barbiturate
• Contraindication known about benzodiazepines (severe respiratory failure, severe acute hepatic failure, myasthenia, syndrome of sleep apnea, glaucoma with closed angle

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Département d'Anesthésie - Réanimation - SMUR - Hôpital Lariboisière

Paris, 75010, France

Location

MeSH Terms

Conditions

Status Epilepticus; Epilepsy; Seizures

Interventions

Clonazepam; fosphenytoin; Lorazepam

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Papa GUEYE, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• François CONCINA, MD

  CHU Toulouse - Hôpital Purpan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2013
• First Posted: June 5, 2013
• Study Start: June 26, 2013
• Primary Completion: February 23, 2018
• Study Completion: February 23, 2018
• Last Updated: October 11, 2018

Record last verified: 2018-10

Locations

FR (1)