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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01359332
First received: May 23, 2011
Last updated: November 6, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Convulsive Status EPILEPTICUS
Procedure: Moderate hypothermia
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Functional impairment at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]

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

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



Secondary Outcome Measures:
  • mortality [ Time Frame: hospital discharge ] [ Designated as safety issue: Yes ]
  • incidence of functional sequelae [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • length of hospital stay [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 270
Study Start Date: December 2010
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: hypothermia Procedure: Moderate hypothermia
procedure of moderate hypothermia therapy, between 32 ° and 34 ° C for 24 hours
Other Name: Moderate hypothermia
No Intervention: control

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01359332

Contacts
Contact: Stéphane LEGRIEL, MD 33(1)39638839 slegriel@ch-versailles.fr

Locations
France
Hôpital André MIGNOT- Service de réanimation médico-chirurgical Recruiting
Le Chesnay, France, 78150
Contact: Stéphane LEGRIEL, MD    33(0)1 39 63 88 39    slegriel@ch-versailles.fr   
Principal Investigator: Stéphane LEGRIEL, MD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Stéphane LEGRIEL, MD, Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01359332     History of Changes
Other Study ID Numbers: P081249
Study First Received: May 23, 2011
Last Updated: November 6, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Convulsive status EPILEPTICUS
hypothermia therapy
convulsive status EPILEPTICUS
(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)

Additional relevant MeSH terms:
Hypothermia
Status Epilepticus
Body Temperature Changes
Brain Diseases
Central Nervous System Diseases
Epilepsy
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on November 20, 2014