Convulsive Status EPILEPTICUSPhase 3HYBERNATUSNCT01359332
Evaluation of Therapeutic Hypothermia in Convulsive Status EPILEPTICUS in Adults in Intensive Care
A Phase 3 study testing Moderate hypothermia in people with Convulsive Status EPILEPTICUS, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Convulsive Status EPILEPTICUS
- What is being tested?
- Moderate hypothermia
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2010to Aug 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Hôpital André MIGNOT- Service de réanimation médico-chirurgical
Le Chesnay, 78150
About this study
Official title: Evaluation of the Interests of a Therapeutic Hypothermia Procedure in Convulsive Status EPILEPTICUS in Adults in Intensive Care - HYBERNATUS Study
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.
Read the 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.
- Conditions
- Convulsive Status EPILEPTICUS
- Being tested
- Moderate hypothermia
- 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)
- Medical subject headings
- Status Epilepticus, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Moderate hypothermiaProcedure or surgery
procedure of moderate hypothermia therapy, between 32 ° and 34 ° C for 24 hours
| Study group | Role | What they receive |
|---|---|---|
| hypothermia | Experimental | Not described Receives: Procedure: Moderate hypothermia |
| control | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 3 months
Secondary outcomes (9)
mortality
Measured: hospital discharge
mortality
Measured: ICU discharge
mortality
Measured: 90 days
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).
Measured: 3 months
length of icu stay
Measured: 3 months
length of hospital stay
Measured: 3 months
Percentages of convulsive and non-convulsive seizure recurrences
Progression to status epilepticus
Measured: 6 to 12 hours
Seizure duration in minutes
Measured: 3 days
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)
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2011 (estimated)
- Study startDec 2010
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Convulsive Status EPILEPTICUSStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 270 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stéphane LEGRIEL, MD,, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01359332
- Sponsor's protocol ID
- P081249
- Acronym
- HYBERNATUS
- Status last verified
- Sep 2016
- First submitted
- 23 May 2011
- Last updated
- 29 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Jacq G, Crepon B, Resche-Rigon M, Schenck M, Geeraerts T, Meziani F, Megarbane B, Chaffaut C, Cariou A, Legriel S. Clinician-Reported Physical and Cognitive Impairments After Convulsive Status Epilepticus: Post Hoc Study of a Randomized Controlled Trial. Neurocrit Care. 2024 Apr;40(2):495-505. doi: 10.1007/s12028-023-01758-6. Epub 2023 Jun 7.
PubMed 37286846Fontaine 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.
PubMed 32913029Legriel 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.
PubMed 28002714Legriel 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.
PubMed 27325409
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Interests of a Therapeutic Hypothermia Procedure in Convulsive Status EPILEPTICUS in Adults in Intensive Care - HYBERNATUS Study
- ClinicalTrials.gov ID
- NCT01359332
- Acronym / sponsor ID
- HYBERNATUS / P081249
- Conditions
- 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)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 270 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Dec 2010
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 24 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| hypothermia | Experimental | Procedure: Moderate hypothermia |
| control | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Moderate hypothermiaprocedure of moderate hypothermia therapy, between 32 ° and 34 ° C for 24 hours | Procedure or surgery | hypothermia |
Primary outcome
Functional impairment at 3 months
Time frame: 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)
9 secondary outcomes
mortality
Time frame: hospital discharge
mortality
Time frame: ICU discharge
mortality
Time frame: 90 days
Incidence of functional sequelae
Time frame: 3 months
length of icu stay
Time frame: 3 months
length of hospital stay
Time frame: 3 months
Percentages of convulsive and non-convulsive seizure recurrences
Time frame: 6 to 12 hours
Seizure duration in minutes
Time frame: 3 days
Percentage of refractory status epilepticus cases
Time frame: 3 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
- Derived from this study: PubMed 37286846Jacq G, Crepon B, Resche-Rigon M, Schenck M, Geeraerts T, Meziani F, Megarbane B, Chaffaut C, Cariou A, Legriel S. Clinician-Reported Physical and Cognitive Impairments After Convulsive Status Epilepticus: Post Hoc Study of a Randomized Controlled Trial. Neurocrit Care. 2024 Apr;40(2):495-505. doi: 10.1007/s12028-023-01758-6. Epub 2023 Jun 7.
- Derived from this study: PubMed 32913029Fontaine 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.
- Derived from this study: PubMed 28002714Legriel 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.
- Derived from this study: PubMed 27325409Legriel 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stéphane LEGRIEL, MD, principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Moderate hypothermia in people with Convulsive Status EPILEPTICUS, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional impairment at 3 months (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01359332, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2016.