IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis

Phase 4

Terminated

• Conditions: Bacterial Meningitis
• Interventions: Procedure: Mild induced hypothermia (32-34°C); Procedure: local recommendations and guidelines

• Registration Number: NCT00774631
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

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 Timeline

• Study First Submitted: 2008-10-16
• Study First Submitted QC: 2008-10-16
• Study First Posted: 2008-10-17
• Study Start: 2009-03
• Primary Completion: 2012-02
• Status Verified: 2012-07
• Study Completion: 2012-07
• Last Update Submitted: 2012-09-14
• Last Update Posted: 2012-09-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hypothermia	Mild induced hypothermia (32-34°C)	mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming
No hypothermia	local recommendations and guidelines	no hypothermia, according to local recommendations and guidelines of medical societies and literature

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Hopital Bichat Claude Bernard; 🇫🇷 Paris, France