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

Primary Purpose

Status Epilepticus, Epilepsy

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Clonazepam
Fosphenytoin
Placebo
Lorazepam
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Status Epilepticus focused on measuring status epilepticus, epilepsy, seizures, convulsive seizures, convulsions, benzodiazepines, anticonvulsants

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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:

    1. 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
    2. if they were having more than 2 repeated convulsive seizures at the time of treatment without regaining consciousness

Exclusion Criteria:

  • 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
  • Contraindication known about fosphenytoin (intermittent acute porphyry)
  • Contraindication known about barbiturate (porphyry, severe respiratory failure, current treatment by saquinavir, ifosfamide and voriconazole, in association with millepertuis)
  • Person unaffiliated in a National Social Security Insurance
  • Pregnant or breast-feeding Woman
  • Impossibility to put an intravenous or intra-osseous catheter for the treatment injection
  • Absence of nurse in the mobile intensive care unit.

Sites / Locations

  • Département d'Anesthésie - Réanimation - SMUR - Hôpital Lariboisière

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

1: Lorazepam + Placebo

2: Clonazepam + Placebo

3: Clonazepam + Fosphenytoin

Arm Description

[ 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

[ 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

[ 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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Duration between the first cessation and the recurrence of seizures
Duration between the first cessation and the recurrence of seizures
Percentage of patients having had a second injection of benzodiazepine
Percentage of patients having had a second injection of benzodiazepine
Percentage of patients having had an injection of the second line treatment
Percentage of patients having had an injection of the second line treatment (i.e. Fosphenytoin or barbiturate)
Percentage of patients having a general anesthesia for refractory status epilepticus
Percentage of patients having a general anesthesia for refractory status epilepticus
Percentage of patients having had a side effect
Percentage of patients having had a side effect (low blood pressure, arrhythmias)
Percentage of patients having been mechanically ventilated
Percentage of patients having been mechanically ventilated in pre-hospital setting
Glasgow Coma Scale
Glasgow Coma Scale on arrival at the hospital
Mortality
Mortality in pre-hospital setting
Mortality
Mortality in hospital until J30 (if the patient still hospitalized)
Length of stay in Intensive Care Unit
Length of stay in Intensive Care Unit
Length of stay in hospital
Length of stay in hospital

Full Information

First Posted
June 3, 2013
Last Updated
October 10, 2018
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT01870024
Brief Title
Comparison Between Lorazepam, Clonazepam and Clonazepam + Fosphenytoin for the Treatment of Out-of-hospital Generalized Status Epilepticus
Acronym
LORACLOFT
Official Title
Comparison Between Lorazepam, Clonazepam and Clonazepam + Fosphenytoin for the Treatment of Out-of-hospital Generalized Status Epilepticus in Adults Patients
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
June 26, 2013 (Actual)
Primary Completion Date
February 23, 2018 (Actual)
Study Completion Date
February 23, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Background: Early and rapid termination of status epilepticus with intravenous administration of benzodiazepines only or its association with other antiepileptic drug improves outcomes. Our out-of-hospital study aims to demonstrate on one hand the superiority of lorazepam compared with clonazepam and on the other hand the efficacy at least equivalent of lorazepam in comparison with the association clonazepam + fosphenytoin. If these hypotheses are demonstrated, the out-of-hospital treatment of the status epilepticus by lorazepam in monotherapy would then be strongly recommended, considering its efficacy and the simplicity of administration in the context of the pre-hospital emergency.Objective: To compare the efficacy of Lorazepam with that of Clonazepam and its association with Fosphenytoin for the treatment of out-of-hospital status epilepticus. Participating centers: 41 prehospital emergency services employing mobile intensive care units and located in urban areas in France participated in this study. In France, the management of out-of-hospital medical emergencies is under the responsibility of the Service d'Aide Medicale Urgente (SAMU). Mobile intensive care units are staffed by an attending emergency physician or anesthesiologist, a nurse, and an ambulance driver. The study is coordinated by the prehospital emergency service of Lariboisiere Hospital, University Paris 7 (Paris, France) Number of patients: 522 patients; 174 patients by group. Duration of the study: The total duration planned is of 48 months Intermediate analysis: An intermediate analysis is planned while 261 patients will be included (50 % of the inclusions).Duration of participation of every patient: 24 hours Data collection: prehospital data recording during the 60 min period of the study, and intrahospital data recording by the medical report of hospitalization. Methodology: Multicenter, randomized, double-blind trial with 3 arms. Main criteria of evaluation: the cessation of the status epilepticus and the absence of recurrence from T20 minutes until T60 minutes after the beginning of the treatment. The cessation of the status epilepticus is defined by the stop of any motor activity and any seizures or convulsive movements. The absence of recurrence is defined by the not occurrence of a new seizures after a period of cessation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Status Epilepticus, Epilepsy
Keywords
status epilepticus, epilepsy, seizures, convulsive seizures, convulsions, benzodiazepines, anticonvulsants

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
434 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1: Lorazepam + Placebo
Arm Type
Active Comparator
Arm Description
[ 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
Arm Title
2: Clonazepam + Placebo
Arm Type
Active Comparator
Arm Description
[ 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
Arm Title
3: Clonazepam + Fosphenytoin
Arm Type
Active Comparator
Arm Description
[ 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
Intervention Type
Drug
Intervention Name(s)
Clonazepam
Intervention Description
clonazepam 0,015 mg/kg
Intervention Type
Drug
Intervention Name(s)
Fosphenytoin
Intervention Description
fosphenytoin 20 mg/kg Equivalent Phenytoin (EP) by intravenous infusion over a period of 15 minutes
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo 20 mg/kg by intravenous infusion over a period of 15 minutes
Intervention Type
Drug
Intervention Name(s)
Lorazepam
Intervention Description
lorazepam 0,1mg/kg by intravenous injection over a period of 2 to 3 minutes)
Primary Outcome Measure Information:
Title
Percentage of patient with a cessation of seizures and absence of recurrence
Description
Percentage of patient with a cessation of seizures and absence of recurrence from 20 minutes until 60 minutes after the beginning of the treatment
Time Frame
between 20 and 60 minutes after the beginning of the treatment
Secondary Outcome Measure Information:
Title
Duration between the first cessation and the recurrence of seizures
Description
Duration between the first cessation and the recurrence of seizures
Time Frame
up to 60 minutes
Title
Percentage of patients having had a second injection of benzodiazepine
Description
Percentage of patients having had a second injection of benzodiazepine
Time Frame
up to 60 minutes
Title
Percentage of patients having had an injection of the second line treatment
Description
Percentage of patients having had an injection of the second line treatment (i.e. Fosphenytoin or barbiturate)
Time Frame
up to 60 minutes
Title
Percentage of patients having a general anesthesia for refractory status epilepticus
Description
Percentage of patients having a general anesthesia for refractory status epilepticus
Time Frame
up to 60 minutes
Title
Percentage of patients having had a side effect
Description
Percentage of patients having had a side effect (low blood pressure, arrhythmias)
Time Frame
up to 60 minutes
Title
Percentage of patients having been mechanically ventilated
Description
Percentage of patients having been mechanically ventilated in pre-hospital setting
Time Frame
up to 60 minutes
Title
Glasgow Coma Scale
Description
Glasgow Coma Scale on arrival at the hospital
Time Frame
60 minutes
Title
Mortality
Description
Mortality in pre-hospital setting
Time Frame
up to 60 minutes
Title
Mortality
Description
Mortality in hospital until J30 (if the patient still hospitalized)
Time Frame
up to Day 30
Title
Length of stay in Intensive Care Unit
Description
Length of stay in Intensive Care Unit
Time Frame
up to Day 30
Title
Length of stay in hospital
Description
Length of stay in hospital
Time Frame
up to Day 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Contraindication known about fosphenytoin (intermittent acute porphyry) Contraindication known about barbiturate (porphyry, severe respiratory failure, current treatment by saquinavir, ifosfamide and voriconazole, in association with millepertuis) Person unaffiliated in a National Social Security Insurance Pregnant or breast-feeding Woman Impossibility to put an intravenous or intra-osseous catheter for the treatment injection Absence of nurse in the mobile intensive care unit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Papa GUEYE, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
François CONCINA, MD
Organizational Affiliation
CHU Toulouse - Hôpital Purpan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Département d'Anesthésie - Réanimation - SMUR - Hôpital Lariboisière
City
Paris
ZIP/Postal Code
75010
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

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