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

NCT01359332 | Completed Phase 3

• 1 other identifier: P081249
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (1)

• 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)

  3 months

Secondary Outcomes (9)

• mortality

  hospital discharge

• mortality

  ICU discharge

• mortality

  90 days

• Incidence of functional sequelae

  3 months

• length of icu stay

  3 months

Study Arms (2)

hypothermia

EXPERIMENTAL

Procedure: Moderate hypothermia

control

NO INTERVENTION

Interventions

Moderate hypothermia PROCEDURE

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

hypothermia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• not affiliation to a social insurance

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital André MIGNOT- Service de réanimation médico-chirurgical

Le Chesnay, 78150, France

Location

Related Publications (4)

• 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.

  PMID: 37286846 DERIVED

• 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.

  PMID: 32913029 DERIVED

• 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.

  PMID: 28002714 DERIVED

• 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.

  PMID: 27325409 DERIVED

MeSH Terms

Conditions

Status Epilepticus; Seizures

Interventions

Hypothermia, Induced

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cryotherapy; Therapeutics

Study Officials

• Stéphane LEGRIEL, MD,

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2011
• First Posted: May 24, 2011
• Study Start: December 1, 2010
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: September 29, 2016

Record last verified: 2016-09

Locations

FR (1)