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Trial record 62 of 107 for:    PHENYTOIN

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

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ClinicalTrials.gov Identifier: NCT01870024
Recruitment Status : Completed
First Posted : June 5, 2013
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease Intervention/treatment Phase
Status Epilepticus Epilepsy Drug: Clonazepam Drug: Fosphenytoin Drug: Placebo Drug: Lorazepam Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 434 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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
Actual Study Start Date : June 26, 2013
Actual Primary Completion Date : February 23, 2018
Actual Study Completion Date : February 23, 2018


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Duration between the first cessation and the recurrence of seizures [ Time Frame: up to 60 minutes ]
    Duration between the first cessation and the recurrence of seizures

  2. Percentage of patients having had a second injection of benzodiazepine [ Time Frame: up to 60 minutes ]
    Percentage of patients having had a second injection of benzodiazepine

  3. Percentage of patients having had an injection of the second line treatment [ Time Frame: up to 60 minutes ]
    Percentage of patients having had an injection of the second line treatment (i.e. Fosphenytoin or barbiturate)

  4. Percentage of patients having a general anesthesia for refractory status epilepticus [ Time Frame: up to 60 minutes ]
    Percentage of patients having a general anesthesia for refractory status epilepticus

  5. Percentage of patients having had a side effect [ Time Frame: up to 60 minutes ]
    Percentage of patients having had a side effect (low blood pressure, arrhythmias)

  6. Percentage of patients having been mechanically ventilated [ Time Frame: up to 60 minutes ]
    Percentage of patients having been mechanically ventilated in pre-hospital setting

  7. Glasgow Coma Scale [ Time Frame: 60 minutes ]
    Glasgow Coma Scale on arrival at the hospital

  8. Mortality [ Time Frame: up to 60 minutes ]
    Mortality in pre-hospital setting

  9. Mortality [ Time Frame: up to Day 30 ]
    Mortality in hospital until J30 (if the patient still hospitalized)

  10. Length of stay in Intensive Care Unit [ Time Frame: up to Day 30 ]
    Length of stay in Intensive Care Unit

  11. Length of stay in hospital [ Time Frame: up to Day 30 ]
    Length of stay in hospital



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01870024


Locations
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France
Département d'Anesthésie - Réanimation - SMUR - Hôpital Lariboisière
Paris, France, 75010
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Papa GUEYE, MD, PhD Assistance Publique - Hôpitaux de Paris
Principal Investigator: François CONCINA, MD CHU Toulouse - Hôpital Purpan

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01870024     History of Changes
Other Study ID Numbers: P110123
2012-003795-39 ( EudraCT Number )
First Posted: June 5, 2013    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018

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

Additional relevant MeSH terms:
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Phenytoin
Epilepsy
Status Epilepticus
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Seizures
Neurologic Manifestations
Signs and Symptoms
Lorazepam
Clonazepam
Fosphenytoin
Anticonvulsants
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Sodium Channel Blockers
Membrane Transport Modulators
Voltage-Gated Sodium Channel Blockers