IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Terminated

CT.gov ID

NCT00774631

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Meningitis	Procedure: Mild induced hypothermia (32-34°C) Procedure: local recommendations and guidelines	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

98 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Mild Induced Hypothermia to Treat Severe Community Acquired Meningitis in Adults Admitted to Intensive Care Unit

Study Start Date :

Mar 1, 2009

Actual Primary Completion Date :

Feb 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hypothermia mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming	Procedure: Mild induced hypothermia (32-34°C) 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.
Active Comparator: No hypothermia no hypothermia, according to local recommendations and guidelines of medical societies and literature	Procedure: local recommendations and guidelines 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.

Arm

Intervention/Treatment

Experimental: Hypothermia

mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming

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

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.

Active Comparator: No hypothermia

no hypothermia, according to local recommendations and guidelines of medical societies and literature

Procedure: local recommendations and guidelines

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.

Outcome Measures

Primary Outcome Measures

Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission. [3 months]

Secondary Outcome Measures

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 [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.