Evaluation of Therapeutic Hypothermia in Convulsive Status EPILEPTICUS in Adults in Intensive Care (HYBERNATUS)
Primary Purpose
Convulsive Status EPILEPTICUS
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Moderate hypothermia
Sponsored by
About this trial
This is an interventional treatment trial for Convulsive Status EPILEPTICUS focused on measuring Convulsive status EPILEPTICUS, hypothermia therapy, (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)
Eligibility 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
Sites / Locations
- Hôpital André MIGNOT- Service de réanimation médico-chirurgical
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
hypothermia
control
Arm Description
Outcomes
Primary Outcome Measures
Functional impairment at 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
mortality
mortality
Incidence of functional sequelae
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
length of hospital stay
Percentages of convulsive and non-convulsive seizure recurrences
Progression to status epilepticus
Seizure duration in minutes
Percentage of refractory status epilepticus cases
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)
Full Information
NCT ID
NCT01359332
First Posted
May 23, 2011
Last Updated
September 28, 2016
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT01359332
Brief Title
Evaluation of Therapeutic Hypothermia in Convulsive Status EPILEPTICUS in Adults in Intensive Care
Acronym
HYBERNATUS
Official Title
Evaluation of the Interests of a Therapeutic Hypothermia Procedure in Convulsive Status EPILEPTICUS in Adults in Intensive Care - HYBERNATUS Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Data Monitoring Committee
No
5. 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 ° 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Convulsive Status EPILEPTICUS
Keywords
Convulsive status EPILEPTICUS, hypothermia therapy, (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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
270 (Actual)
8. Arms, Groups, and Interventions
Arm Title
hypothermia
Arm Type
Experimental
Arm Title
control
Arm Type
No Intervention
Intervention Type
Procedure
Intervention Name(s)
Moderate hypothermia
Intervention Description
procedure of moderate hypothermia therapy, between 32 ° and 34 ° C for 24 hours
Primary Outcome Measure Information:
Title
Functional impairment at 3 months
Description
Functional impairment is defined by a Glasgow Outcome Scale strictly less than 5.
The time of evaluation should be 3 months (+/- 1 week)
Time Frame
3 months
Secondary Outcome Measure Information:
Title
mortality
Time Frame
hospital discharge
Title
mortality
Time Frame
ICU discharge
Title
mortality
Time Frame
90 days
Title
Incidence of functional sequelae
Description
Judged on the frequency of seizures, the recurrence of epileptic status after hospitalization, the number of anti-epileptic drug, mini mental score (MMS).
Time Frame
3 months
Title
length of icu stay
Time Frame
3 months
Title
length of hospital stay
Time Frame
3 months
Title
Percentages of convulsive and non-convulsive seizure recurrences
Description
Progression to status epilepticus
Time Frame
6 to 12 hours
Title
Seizure duration in minutes
Time Frame
3 days
Title
Percentage of refractory status epilepticus cases
Description
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)
Time Frame
3 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stéphane LEGRIEL, MD,
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital André MIGNOT- Service de réanimation médico-chirurgical
City
Le Chesnay
ZIP/Postal Code
78150
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
32913029
Citation
Fontaine C, Lemiale V, Resche-Rigon M, Schenck M, Chelly J, Geeraerts T, Hamdi A, Guitton C, Meziani F, Lefrant JY, Megarbane B, Mentec H, Chaffaut C, Cariou A, Legriel S; HYBERNATUS Study Group. Association of systemic secondary brain insults and outcome in patients with convulsive status epilepticus: A post hoc study of a randomized controlled trial. Neurology. 2020 Nov 3;95(18):e2529-e2541. doi: 10.1212/WNL.0000000000010726. Epub 2020 Sep 10.
Results Reference
derived
PubMed Identifier
28002714
Citation
Legriel S, Lemiale V, Schenck M, Chelly J, Laurent V, Daviaud F, Srairi M, Hamdi A, Geri G, Rossignol T, Hilly-Ginoux J, Boisrame-Helms J, Louart B, Malissin I, Mongardon N, Planquette B, Thirion M, Merceron S, Canet E, Pico F, Tran-Dinh YR, Bedos JP, Azoulay E, Resche-Rigon M, Cariou A; HYBERNATUS Study Group. Hypothermia for Neuroprotection in Convulsive Status Epilepticus. N Engl J Med. 2016 Dec 22;375(25):2457-2467. doi: 10.1056/NEJMoa1608193.
Results Reference
derived
PubMed Identifier
27325409
Citation
Legriel S, Pico F, Tran-Dinh YR, Lemiale V, Bedos JP, Resche-Rigon M, Cariou A. Neuroprotective effect of therapeutic hypothermia versus standard care alone after convulsive status epilepticus: protocol of the multicentre randomised controlled trial HYBERNATUS. Ann Intensive Care. 2016 Dec;6(1):54. doi: 10.1186/s13613-016-0159-z. Epub 2016 Jun 21.
Results Reference
derived
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Evaluation of Therapeutic Hypothermia in Convulsive Status EPILEPTICUS in Adults in Intensive Care
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