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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT01359332

Collaborator

(none)

270

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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 °

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.

Condition or Disease	Intervention/Treatment	Phase
Convulsive Status EPILEPTICUS	Procedure: Moderate hypothermia	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

270 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Evaluation of the Interests of a Therapeutic Hypothermia Procedure in Convulsive Status EPILEPTICUS in Adults in Intensive Care - HYBERNATUS Study

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: hypothermia	Procedure: Moderate hypothermia procedure of moderate hypothermia therapy, between 32 ° and 34 ° C for 24 hours
No Intervention: control

Arm

Intervention/Treatment

Experimental: hypothermia

Procedure: Moderate hypothermia

procedure of moderate hypothermia therapy, between 32 ° and 34 ° C for 24 hours

No Intervention: control

Outcome Measures

Primary Outcome Measures

Functional impairment at 3 months [3 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

mortality [hospital discharge]
mortality [ICU discharge]
mortality [90 days]
Incidence of functional sequelae [3 months]
Judged on the frequency of seizures, the recurrence of epileptic status after hospitalization, the number of anti-epileptic drug, mini mental score (MMS).
length of icu stay [3 months]
length of hospital stay [3 months]
Percentages of convulsive and non-convulsive seizure recurrences [6 to 12 hours]
Progression to status epilepticus
Seizure duration in minutes [3 days]
Percentage of refractory status epilepticus cases [3 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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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