MedPath

Evaluation of Therapeutic Hypothermia in Convulsive Status EPILEPTICUS in Adults in Intensive Care

Phase 3
Completed
Conditions
Convulsive Status EPILEPTICUS
Interventions
Procedure: Moderate hypothermia
Registration Number
NCT01359332
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

Status EPILEPTICUS (SE) is a major medical emergency. The incidence per 100,000 population has been estimated at 9.9 episodes in Europe and 41 episodes in the US. The overall morbidity and mortality associated with convulsive SE (CSE) is 60% at three months. The alteration of functional prognosis of these patients is more conventionally attributed to the cause than to CSE itself. Longer seizure duration, progression to refractory status EPILEPTICUS and presence of cerebral insult are strong factors independently associated with a poor functional outcome. These three factors offer may be amenable to improvement and hope for preventive strategies. Current guidelines recommend the use of anticonvulsant treatment whose goal is prompt cessation of clinical and electrical seizures. None of these treatments has demonstrated NEUROPROTECTICE property. Therapeutic moderate hypothermia (between 32 and 34 ° C) showed interest in neuroprotection of post anoxic coma patients after a cardiovascular arrest on ventricular fibrillation by reducing morbidity and mortality in about 20% without major side effects. This technique has been used successfully in various pathologies such as stroke or traumatic brain injury. Pathophysiological mechanisms involved in epileptogenesis and neurotoxicity induced by persistence of seizures can be blocked by therapeutic hypothermia. Recent work on experimental models of SE demonstrated neuroprotective and anticonvulsant interest of therapeutic hypothermia. Therapeutic hypothermia has also been successfully used in some cases of particularly refractory CSE. Its early use in patients with SE would have a double interest: neuroprotective and anticonvulsant. There is currently no published studies or ongoing to determine the interest of its early use in patients with CSE.

Detailed Description

Status EPILEPTICUS (SE) is a major medical emergency. The incidence per 100,000 population has been estimated at 9.9 episodes in Europe and 41 episodes in the US. The overall morbidity and mortality associated with convulsive SE (CSE) is 60% at three months. The alteration of functional prognosis of these patients is more conventionally attributed to the cause than to CSE itself. Longer seizure duration, progression to refractory status EPILEPTICUS and presence of cerebral insult are strong factors independently associated with a poor functional outcome. These three factors offer may be amenable to improvement and hope for preventive strategies. Current guidelines recommend the use of anticonvulsant treatment whose goal is prompt cessation of clinical and electrical seizures. None of these treatments has demonstrated NEUROPROTECTICE property. Therapeutic moderate hypothermia (between 32 and 34 ° C) showed interest in neuroprotection of post anoxic coma patients after a cardiovascular arrest on ventricular fibrillation by reducing morbidity and mortality in about 20% without major side effects. This technique has been used successfully in various pathologies such as stroke or traumatic brain injury. Pathophysiological mechanisms involved in epileptogenesis and neurotoxicity induced by persistence of seizures can be blocked by therapeutic hypothermia. Recent work on experimental models of SE demonstrated neuroprotective and anticonvulsant interest of therapeutic hypothermia. Therapeutic hypothermia has also been successfully used in some cases of particularly refractory CSE. Its early use in patients with SE would have a double interest: neuroprotective and anticonvulsant. There is currently no published studies or ongoing to determine the interest of its early use in patients with CSE.

Thus, the current study AIMAS at evaluating the effectiveness of the implementation of a procedure of moderate hypothermia therapy, between 32 ° and 34 ° C for 24 hours, to reduce morbidity and mortality at 3 months (+ / - 1 week) in mechanically ventilated ICU patients with convulsive status EPILEPTICUS.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
270
Inclusion Criteria
  • patient age ≥ 18 years
  • patient hospitalized in intensive care unit
  • patient already under mechanical ventilation
  • patient who presented a convulsive status EPILEPTICUS episode (defined as continuous SEIZURING for longer than 5 min or three seizures not separated by recovery of normal consciousness or of the level of consciousness present before the seizures)
  • whose motor manifestations had begun less than 8 hours before randomization
  • after having informed written consent signed by a parent or a close if present.
Exclusion Criteria
  • patients with full recovery, postanoxic status EPILEPTICUS after cardia arrest
  • convulsive status EPILEPTICUS for which an intervention (neurosurgical or other) is urgently needed not allowing the application of the procedure for therapeutic hypothermia
  • dying patient, limitations in care, or whose life expectancy is estimated at baseline of less than 1 year
  • patients whose follow-up to 3 months (+ / - 1 week) seems a PRIORI not possible
  • pregnant women (pregnancy positive urine test or known before inclusion),
  • participation in another biomedical therapeutic intervention whose primary endpoint was not reached at inclusion in HYBERNATUS study
  • not affiliation to a social insurance

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
hypothermiaModerate hypothermia-
Primary Outcome Measures
NameTimeMethod
Functional impairment at 3 months3 months

Functional impairment is defined by a Glasgow Outcome Scale strictly less than 5.

The time of evaluation should be 3 months (+/- 1 week)

Secondary Outcome Measures
NameTimeMethod
length of icu stay3 months
length of hospital stay3 months
Percentages of convulsive and non-convulsive seizure recurrences6 to 12 hours

Progression to status epilepticus

Seizure duration in minutes3 days
Percentage of refractory status epilepticus cases3 days

Judged on the frequency of seizures within 24 hours after status epilepticus onset (refractory status epilepticus on day 1) and on the frequency of seizures within 48 hours after anesthetic treatment withdrawal (super refractory status epilepticus)

mortality90 days
Incidence of functional sequelae3 months

Judged on the frequency of seizures, the recurrence of epileptic status after hospitalization, the number of anti-epileptic drug, mini mental score (MMS).

Trial Locations

Locations (1)

Hôpital André MIGNOT- Service de réanimation médico-chirurgical

🇫🇷

Le Chesnay, France

© Copyright 2025. All Rights Reserved by MedPath