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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01870024
First received: June 3, 2013
Last updated: July 26, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Status Epilepticus
Epilepsy
Drug: Clonazepam
Drug: Fosphenytoin
Drug: Placebo
Drug: Lorazepam
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Comparison Between Lorazepam, Clonazepam and Clonazepam + Fosphenytoin for the Treatment of Out-of-hospital Generalized Status Epilepticus in Adults Patients

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Percentage of patient with a cessation of seizures and absence of recurrence [ Time Frame: between 20 and 60 minutes after the beginning of the treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: up to 60 minutes ] [ Designated as safety issue: No ]
    Duration between the first cessation and the recurrence of seizures

  • Percentage of patients having had a second injection of benzodiazepine [ Time Frame: up to 60 minutes ] [ Designated as safety issue: No ]
    Percentage of patients having had a second injection of benzodiazepine

  • Percentage of patients having had an injection of the second line treatment [ Time Frame: up to 60 minutes ] [ Designated as safety issue: No ]
    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 [ Time Frame: up to 60 minutes ] [ Designated as safety issue: No ]
    Percentage of patients having a general anesthesia for refractory status epilepticus

  • Percentage of patients having had a side effect [ Time Frame: up to 60 minutes ] [ Designated as safety issue: No ]
    Percentage of patients having had a side effect (low blood pressure, arrhythmias)

  • Percentage of patients having been mechanically ventilated [ Time Frame: up to 60 minutes ] [ Designated as safety issue: No ]
    Percentage of patients having been mechanically ventilated in pre-hospital setting

  • Glasgow Coma Scale [ Time Frame: 60 minutes ] [ Designated as safety issue: No ]
    Glasgow Coma Scale on arrival at the hospital

  • Mortality [ Time Frame: up to 60 minutes ] [ Designated as safety issue: No ]
    Mortality in pre-hospital setting

  • Mortality [ Time Frame: up to Day 30 ] [ Designated as safety issue: No ]
    Mortality in hospital until J30 (if the patient still hospitalized)

  • Length of stay in Intensive Care Unit [ Time Frame: up to Day 30 ] [ Designated as safety issue: No ]
    Length of stay in Intensive Care Unit

  • Length of stay in hospital [ Time Frame: up to Day 30 ] [ Designated as safety issue: No ]
    Length of stay in hospital


Estimated Enrollment: 522
Study Start Date: June 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1: Lorazepam + Placebo
[ 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
placebo 20 mg/kg by intravenous infusion over a period of 15 minutes
Drug: Lorazepam
lorazepam 0,1mg/kg by intravenous injection over a period of 2 to 3 minutes)
Active Comparator: 2: Clonazepam + Placebo
[ 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
clonazepam 0,015 mg/kg
Drug: Placebo
placebo 20 mg/kg by intravenous infusion over a period of 15 minutes
Active Comparator: 3: Clonazepam + Fosphenytoin
[ 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
clonazepam 0,015 mg/kg
Drug: Fosphenytoin
fosphenytoin 20 mg/kg Equivalent Phenytoin (EP) by intravenous infusion over a period of 15 minutes

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: 38 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 24 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01870024

Contacts
Contact: Papa GUEYE, MD 33 1 49 95 61 61 papa.gueye@lrb.aphp.fr
Contact: François CONCINA, MD 33 5 67 69 16 75 concina.f@chu-toulouse.fr

Locations
France
Département d'Anesthésie - Réanimation - SMUR - Hôpital Lariboisière Recruiting
Paris, France, 75010
Contact: Papa GUEYE, MD, PhD    33 1 49 95 61 61    papa.gueye@lrb.aphp.fr   
Principal Investigator: Papa GUEYE, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Papa GUEYE, MD, PhD Assistance Publique - Hôpitaux de Paris
Principal Investigator: François CONCINA, MD CHU Toulouse - Hôpital Purpan
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01870024     History of Changes
Other Study ID Numbers: P110123, 2012-003795-39
Study First Received: June 3, 2013
Last Updated: July 26, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
status epilepticus
epilepsy
seizures
convulsive seizures
convulsions
benzodiazepines
anticonvulsants

Additional relevant MeSH terms:
Epilepsy
Status Epilepticus
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Fosphenytoin
Clonazepam
Lorazepam
Phenytoin
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 20, 2014