IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis

Bacterial Meningitis Clinical Trial

— IHPOTOTAM  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00774631
• Other study ID #: P 060217
• Secondary ID: AOM 06 038
• Status: Terminated
• Phase: Phase 4
• First received: October 16, 2008
• Last updated: September 14, 2012
• Start date: March 2009
• Est. completion date: July 2012

Study information

• Verified date: July 2012
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of HealthFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 98
• Est. completion date: July 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bacterial Meningitis
• Hypothermia
• Meningitis
• Meningitis, Bacterial

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	Hopital Bichat Claude Bernard	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission.		3 months	No
Secondary	Mortality (assessed on day 14 after admission, day 28, total in-hospital mortality, and at 3 and 6 months)		6 months	Yes
Secondary	ICU length of stay		6 months	No
Secondary	Score on GOS at ICU discharge and 6 months after admission		6 months	No
Secondary	Neurological examination at discharge and 6 months after admission		6 months	No
Secondary	Neuropsychological outcome at 6 months in a subset of centres; patient will be tested with a neuropsychological test battery described previously		6 months	No
Secondary	MRC score on ICU discharge		3 months	No
Secondary	Prevalence of status EPILEPTISIS		6 months	No
Secondary	Prevalence of infections (aspiration pneumonia and nosocomial infections)		6 months	No
Secondary	Potential hypothermia related side effects as cardiac arrhythmia, electrolyte balance, hyperglycemia, bleeding, acute pancreatitis (see definitions further).		6 months	No