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| ID | Type | Description | Link |
|---|---|---|---|
| AOM 06 038 | Other Identifier | French Ministry |
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The sponsor stoppes the study for the security problem.
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Bacterial meningitis is a severe infection of the envelope which surrounds the brain. It is sometimes responsible for a cerebral oedema mattering with a loss of consciousness (coma). The usual treatment of this affection is based on the antibiotic therapy, anti-inflammatory drug and resuscitation measures in intensive care setting but the prognosis of comatose patients remains poor.
Moderate hypothermia (body temperature is downed between 32 and 34°C°) made the proof of its efficiency in certain cerebral pathologies (notably the cerebral distress after cardiac arrest or oxygen lack in neonates) but was never evaluated in meningitis. In meningitis animal studies and in severe traumatic brain injury, moderate hypothermia is able to diminish cerebral oedema and brain inflammation.
Thus, the objective of this study is to compare two strategies: only usual care or usual care completed by moderate hypothermia. The body temperature will be lowered between 32 and 34°C by means of a catheter placed in a big vein and connected to a machine in which circulates a cold liquid, or by means of an external cooling (ice-cold blanket, ice packs placed on the body). Whatever technique is chosen, the technique is perfectly mastered by the teams which take charge of the patients. After 48 hours, the technique of hypothermia will be suspended and body temperature will return passively and gradually to normal.
The investigators believe that moderate hypothermia will improve the prognosis of the most severe patients.
Investigational procedure:
This study evaluates the impact of mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming according to recommendations described in appendix. All treatment will be according to local recommendations and guidelines of medical societies and literature. Physicians are advised to use these recommendations; however, the best treatment option for the individual patient should be used.
Mild Induced hypothermia:
Investigators are advised to use the cooling techniques as used in patients with cardiac arrest. Thus, the choice of cooling method will be left to investigators. Hypothermia will be induced by cold saline infusion as described in appendix 5 [6, 48]. Core temperature will be monitored by oesophageal probe and maintained between 32°C and 34°C during 48 hours and followed by strictly passive rewarming. During this phase of treatment, patients will receive deep sedation associated with neuromuscular blockers. Centers participating to the trial will have expertise in cooling methods.
Controls:
Controls will receive standard care and will be also be deeply sedated for 48 hours.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hypothermia | Experimental | mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming |
|
| No hypothermia | Active Comparator | no hypothermia, according to local recommendations and guidelines of medical societies and literature |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mild induced hypothermia (32-34°C) | Procedure | Mild Induced hypothermia: Investigators are advised to use the cooling techniques as used in patients with cardiac arrest. Thus, the choice of cooling method will be left to investigators. Hypothermia will be induced by cold saline infusion as described in appendix 5 [6, 48]. Core temperature will be monitored by oesophageal probe and maintained between 32°C and 34°C during 48 hours and followed by strictly passive rewarming. During this phase of treatment, patients will receive deep sedation associated with neuromuscular blockers. Centers participating to the trial will have expertise in cooling methods. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission. | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality (assessed on day 14 after admission, day 28, total in-hospital mortality, and at 3 and 6 months) | 6 months | |
| ICU length of stay | 6 months | |
| Score on GOS at ICU discharge and 6 months after admission |
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INCLUSION CRITERIA:
EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| MOURVILLIER Bruno, MD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Bichat Claude Bernard | Paris | 75018 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24105303 | Derived | Mourvillier B, Tubach F, van de Beek D, Garot D, Pichon N, Georges H, Lefevre LM, Bollaert PE, Boulain T, Luis D, Cariou A, Girardie P, Chelha R, Megarbane B, Delahaye A, Chalumeau-Lemoine L, Legriel S, Beuret P, Brivet F, Bruel C, Camou F, Chatellier D, Chillet P, Clair B, Constantin JM, Duguet A, Galliot R, Bayle F, Hyvernat H, Ouchenir K, Plantefeve G, Quenot JP, Richecoeur J, Schwebel C, Sirodot M, Esposito-Farese M, Le Tulzo Y, Wolff M. Induced hypothermia in severe bacterial meningitis: a randomized clinical trial. JAMA. 2013 Nov 27;310(20):2174-83. doi: 10.1001/jama.2013.280506. |
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| ID | Term |
|---|---|
| D016920 | Meningitis, Bacterial |
| D008581 | Meningitis |
| D007035 | Hypothermia |
| ID | Term |
|---|---|
| D020806 | Central Nervous System Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D007036 | Hypothermia, Induced |
| D017408 | Guidelines as Topic |
| ID | Term |
|---|---|
| D017679 | Cryotherapy |
| D013812 | Therapeutics |
| D011785 | Quality Assurance, Health Care |
| D011787 | Quality of Health Care |
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|
| local recommendations and guidelines | Procedure | Investigational procedure: This study evaluates the impact of mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming according to recommendations described in appendix. All treatment will be according to local recommendations and guidelines of medical societies and literature. Physicians are advised to use these recommendations; however, the best treatment option for the individual patient should be used. Controls will receive standard care and will be also be deeply sedated for 48 hours. |
|
| 6 months |
| Neurological examination at discharge and 6 months after admission | 6 months |
| Neuropsychological outcome at 6 months in a subset of centres; patient will be tested with a neuropsychological test battery described previously | 6 months |
| MRC score on ICU discharge | 3 months |
| Prevalence of status EPILEPTISIS | 6 months |
| Prevalence of infections (aspiration pneumonia and nosocomial infections) | 6 months |
| Potential hypothermia related side effects as cardiac arrhythmia, electrolyte balance, hyperglycemia, bleeding, acute pancreatitis (see definitions further). | 6 months |
| D002494 | Central Nervous System Infections |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000090862 | Neuroinflammatory Diseases |
| D001832 | Body Temperature Changes |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006298 |
| Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |