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IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis (IHPOTOTAM)

Primary Purpose

Bacterial Meningitis

Status
Terminated
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Mild induced hypothermia (32-34°C)
local recommendations and guidelines
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bacterial Meningitis focused on measuring Meningitis, Hypothermia, Intensive care

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Hopital Bichat Claude Bernard

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Hypothermia

No hypothermia

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Mortality (assessed on day 14 after admission, day 28, total in-hospital mortality, and at 3 and 6 months)
ICU length of stay
Score on GOS at ICU discharge and 6 months after admission
Neurological examination at discharge and 6 months after admission
Neuropsychological outcome at 6 months in a subset of centres; patient will be tested with a neuropsychological test battery described previously
MRC score on ICU discharge
Prevalence of status EPILEPTISIS
Prevalence of infections (aspiration pneumonia and nosocomial infections)
Potential hypothermia related side effects as cardiac arrhythmia, electrolyte balance, hyperglycemia, bleeding, acute pancreatitis (see definitions further).

Full Information

First Posted
October 16, 2008
Last Updated
September 14, 2012
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT00774631
Brief Title
IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis
Acronym
IHPOTOTAM
Official Title
Mild Induced Hypothermia to Treat Severe Community Acquired Meningitis in Adults Admitted to Intensive Care Unit
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Terminated
Why Stopped
The sponsor stoppes the study for the security problem.
Study Start Date
March 2009 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacterial Meningitis
Keywords
Meningitis, Hypothermia, Intensive care

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
98 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hypothermia
Arm Type
Experimental
Arm Description
mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming
Arm Title
No hypothermia
Arm Type
Active Comparator
Arm Description
no hypothermia, according to local recommendations and guidelines of medical societies and literature
Intervention Type
Procedure
Intervention Name(s)
Mild induced hypothermia (32-34°C)
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
local recommendations and guidelines
Intervention 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. Controls will receive standard care and will be also be deeply sedated for 48 hours.
Primary Outcome Measure Information:
Title
Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Mortality (assessed on day 14 after admission, day 28, total in-hospital mortality, and at 3 and 6 months)
Time Frame
6 months
Title
ICU length of stay
Time Frame
6 months
Title
Score on GOS at ICU discharge and 6 months after admission
Time Frame
6 months
Title
Neurological examination at discharge and 6 months after admission
Time Frame
6 months
Title
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
Title
MRC score on ICU discharge
Time Frame
3 months
Title
Prevalence of status EPILEPTISIS
Time Frame
6 months
Title
Prevalence of infections (aspiration pneumonia and nosocomial infections)
Time Frame
6 months
Title
Potential hypothermia related side effects as cardiac arrhythmia, electrolyte balance, hyperglycemia, bleeding, acute pancreatitis (see definitions further).
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MOURVILLIER Bruno, MD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Bichat Claude Bernard
City
Paris
ZIP/Postal Code
75018
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
24105303
Citation
Mourvillier B, Tubach F, van de Beek D, Garot D, Pichon N, Georges H, Lefevre LM, Bollaert PE, Boulain T, Luis D, Cariou A, Girardie P, Chelha R, Megarbane B, Delahaye A, Chalumeau-Lemoine L, Legriel S, Beuret P, Brivet F, Bruel C, Camou F, Chatellier D, Chillet P, Clair B, Constantin JM, Duguet A, Galliot R, Bayle F, Hyvernat H, Ouchenir K, Plantefeve G, Quenot JP, Richecoeur J, Schwebel C, Sirodot M, Esposito-Farese M, Le Tulzo Y, Wolff M. Induced hypothermia in severe bacterial meningitis: a randomized clinical trial. JAMA. 2013 Nov 27;310(20):2174-83. doi: 10.1001/jama.2013.280506.
Results Reference
derived

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IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis

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