IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis

Assistance Publique - Hôpitaux de Paris

Status and phase

Terminated

Phase 4

Conditions

Bacterial Meningitis

Treatments

Procedure: Mild induced hypothermia (32-34°C)

Procedure: local recommendations and guidelines

Study type

Interventional

Funder types

Other

Identifiers

NCT00774631

P 060217

AOM 06 038 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

98 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Subject is 18 years of age or older
Clinically suspected community-acquired bacterial meningitis (More than 100 white blood cells in CSF and a glucose CSF/Blood ratio of 1/3 or less, or a CSF protein level above 2,2 g/L.)
Presence of micro-organisms on CSF Gram's stain examination
Positive soluble antigen or PCR for S. pneumoniae or N. meningitides
Positive CSF cultures
Score on Glasgow Coma Score < 8
Patient received appropriate antimicrobial therapy (according to recommendations)
If present, legally acceptable representative has provided written and dated informed consent to participate in the study.

Exclusion criteria

Glasgow Coma Score < 8 for more than 12 hours
Patients with HIV positivity: positive cryptococcal antigen in blood or CSF; Cerebral abscess
pregnancy
Subject has been designated as "not full support", "do not resuscitate" or equivalent status which prohibits the use of life supporting interventions thereby limiting options available
Subject admitted for a clinical situation in which induced hypothermia is recommended
Purpura fulminancy, defined as septic shock with extensive necrotizing purpura and disseminated intravascular coagulation.