IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis - Full Text View

Purpose

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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Mild Induced Hypothermia to Treat Severe Community Acquired Meningitis in Adults Admitted to Intensive Care Unit

Resource links provided by NLM:

MedlinePlus related topics: Hypothermia Meningitis

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mortality (assessed on day 14 after admission, day 28, total in-hospital mortality, and at 3 and 6 months) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
ICU length of stay [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Score on GOS at ICU discharge and 6 months after admission [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Neurological examination at discharge and 6 months after admission [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Neuropsychological outcome at 6 months in a subset of centres; patient will be tested with a neuropsychological test battery described previously [ Time Frame: 6 months ] [ Designated as safety issue: No ]
MRC score on ICU discharge [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Prevalence of status EPILEPTISIS [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Prevalence of infections (aspiration pneumonia and nosocomial infections) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Potential hypothermia related side effects as cardiac arrhythmia, electrolyte balance, hyperglycemia, bleeding, acute pancreatitis (see definitions further). [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment:	98
Study Start Date:	March 2009
Study Completion Date:	July 2012
Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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. Other Name: Mild induced hypothermia (32-34°C)
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. Other Name: local recommendations and guidelines

Arms

Assigned Interventions

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.

Other Name: Mild induced hypothermia (32-34°C)

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.

Other Name: local recommendations and guidelines

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00774631

Locations

France
Hopital Bichat Claude Bernard
Paris, France, 75018

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator:

MOURVILLIER Bruno, MD

Assistance Publique - Hôpitaux de Paris

More Information

No publications provided

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00774631 History of Changes
Other Study ID Numbers:	P 060217, AOM 06 038
Study First Received:	October 16, 2008
Last Updated:	September 14, 2012
Health Authority:	France: Ministry of Health France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Meningitis
Hypothermia
Intensive care

Additional relevant MeSH terms:

Hypothermia
Meningitis
Meningitis, Bacterial
Body Temperature Changes
Signs and Symptoms

Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on May 21, 2013