Comparison Between Lorazepam, Clonazepam and Clonazepam + Fosphenytoin for the Treatment of Out-of-hospital Generalized Status Epilepticus
Information source: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Status Epilepticus; Epilepsy
Intervention: Clonazepam (Drug); Fosphenytoin (Drug); Placebo (Drug); Lorazepam (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Assistance Publique - Hôpitaux de Paris Official(s) and/or principal investigator(s): Papa GUEYE, MD, PhD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris François CONCINA, MD, Principal Investigator, Affiliation: CHU Toulouse - Hôpital Purpan
Overall contact: Papa GUEYE, MD, Phone: 33 1 49 95 61 61, Email: papa.gueye@lrb.aphp.fr
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.
Clinical Details
Official title: Comparison Between Lorazepam, Clonazepam and Clonazepam + Fosphenytoin for the Treatment of Out-of-hospital Generalized Status Epilepticus in Adults Patients
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Percentage of patient with a cessation of seizures and absence of recurrence
Secondary outcome: Duration between the first cessation and the recurrence of seizuresPercentage 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 a general anesthesia for refractory status epilepticus Percentage of patients having had a side effect Percentage of patients having been mechanically ventilated Glasgow Coma Scale Mortality Mortality Length of stay in Intensive Care Unit Length of stay in hospital
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Papa GUEYE, MD, Phone: 33 1 49 95 61 61, Email: papa.gueye@lrb.aphp.fr
Département d'Anesthésie - Réanimation - SMUR - Hôpital Lariboisière, Paris 75010, France; Recruiting Papa GUEYE, MD, PhD, Phone: 33 1 49 95 61 61, Email: papa.gueye@lrb.aphp.fr Papa GUEYE, MD, PhD, Principal Investigator
Additional Information
Starting date: June 2013
Last updated: July 26, 2013
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