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IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis (IHPOTOTAM)

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ClinicalTrials.gov Identifier: NCT00774631
Recruitment Status : Terminated (The sponsor stoppes the study for the security problem.)
First Posted : October 17, 2008
Last Update Posted : September 17, 2012
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE October 16, 2008
First Posted Date  ICMJE October 17, 2008
Last Update Posted Date September 17, 2012
Study Start Date  ICMJE March 2009
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2008)
Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission. [ Time Frame: 3 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00774631 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2008)
  • Mortality (assessed on day 14 after admission, day 28, total in-hospital mortality, and at 3 and 6 months) [ Time Frame: 6 months ]
  • ICU length of stay [ Time Frame: 6 months ]
  • Score on GOS at ICU discharge and 6 months after admission [ Time Frame: 6 months ]
  • Neurological examination at discharge and 6 months after admission [ Time Frame: 6 months ]
  • 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 ]
  • MRC score on ICU discharge [ Time Frame: 3 months ]
  • Prevalence of status EPILEPTISIS [ Time Frame: 6 months ]
  • Prevalence of infections (aspiration pneumonia and nosocomial infections) [ Time Frame: 6 months ]
  • Potential hypothermia related side effects as cardiac arrhythmia, electrolyte balance, hyperglycemia, bleeding, acute pancreatitis (see definitions further). [ Time Frame: 6 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis
Official Title  ICMJE Mild Induced Hypothermia to Treat Severe Community Acquired Meningitis in Adults Admitted to Intensive Care Unit
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 Type  ICMJE Interventional
Study Phase Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Bacterial Meningitis
Intervention  ICMJE
  • 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.

  • 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.

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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 9, 2012)
98
Original Estimated Enrollment  ICMJE
 (submitted: October 16, 2008)
318
Actual Study Completion Date July 2012
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00774631
Other Study ID Numbers  ICMJE P 060217
AOM 06 038 ( Other Identifier: French Ministry )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: MOURVILLIER Bruno, MD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP