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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003795-39 | EudraCT Number |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clonazepam | Drug | clonazepam 0,015 mg/kg |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Duration between the first cessation and the recurrence of seizures | Duration between the first cessation and the recurrence of seizures | up to 60 minutes |
| Percentage of patients having had a second injection of benzodiazepine |
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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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Papa GUEYE, MD, PhD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| François CONCINA, MD | CHU Toulouse - Hôpital Purpan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Département d'Anesthésie - Réanimation - SMUR - Hôpital Lariboisière | Paris | 75010 | France |
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| Fosphenytoin | Drug | fosphenytoin 20 mg/kg Equivalent Phenytoin (EP) by intravenous infusion over a period of 15 minutes |
|
| Placebo | Drug | placebo 20 mg/kg by intravenous infusion over a period of 15 minutes |
|
| Lorazepam | Drug | lorazepam 0,1mg/kg by intravenous injection over a period of 2 to 3 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 | Percentage of patients having had an injection of the second line treatment (i.e. Fosphenytoin or barbiturate) | up to 60 minutes |
| Percentage of patients having a general anesthesia for refractory status epilepticus | Percentage of patients having a general anesthesia for refractory status epilepticus | up to 60 minutes |
| Percentage of patients having had a side effect | Percentage of patients having had a side effect (low blood pressure, arrhythmias) | up to 60 minutes |
| Percentage of patients having been mechanically ventilated | Percentage of patients having been mechanically ventilated in pre-hospital setting | up to 60 minutes |
| Glasgow Coma Scale | Glasgow Coma Scale on arrival at the hospital | 60 minutes |
| Mortality | Mortality in pre-hospital setting | up to 60 minutes |
| Mortality | Mortality in hospital until J30 (if the patient still hospitalized) | up to Day 30 |
| Length of stay in Intensive Care Unit | Length of stay in Intensive Care Unit | up to Day 30 |
| Length of stay in hospital | Length of stay in hospital | up to Day 30 |
| ID | Term |
|---|---|
| D013226 | Status Epilepticus |
| D004827 | Epilepsy |
| D012640 | Seizures |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D002998 | Clonazepam |
| C043114 | fosphenytoin |
| D008140 | Lorazepam |
| ID | Term |
|---|---|
| D001570 | Benzodiazepinones |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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