- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00774631
IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis (IHPOTOTAM)
Mild Induced Hypothermia to Treat Severe Community Acquired Meningitis in Adults Admitted to Intensive Care Unit
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Paris, France, 75018
- Hopital Bichat Claude Bernard
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Hypothermia
mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming
|
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. |
Active Comparator: No hypothermia
no hypothermia, according to local recommendations and guidelines of medical societies and literature
|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission.
Time Frame: 3 months
|
3 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Mortality (assessed on day 14 after admission, day 28, total in-hospital mortality, and at 3 and 6 months)
Time Frame: 6 months
|
6 months
|
ICU length of stay
Time Frame: 6 months
|
6 months
|
Score on GOS at ICU discharge and 6 months after admission
Time Frame: 6 months
|
6 months
|
Neurological examination at discharge and 6 months after admission
Time Frame: 6 months
|
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
|
6 months
|
MRC score on ICU discharge
Time Frame: 3 months
|
3 months
|
Prevalence of status EPILEPTISIS
Time Frame: 6 months
|
6 months
|
Prevalence of infections (aspiration pneumonia and nosocomial infections)
Time Frame: 6 months
|
6 months
|
Potential hypothermia related side effects as cardiac arrhythmia, electrolyte balance, hyperglycemia, bleeding, acute pancreatitis (see definitions further).
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: MOURVILLIER Bruno, MD, Assistance Publique - Hôpitaux de Paris
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- P 060217
- AOM 06 038 (Other Identifier: French Ministry)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Bacterial Meningitis
-
Rambam Health Care CampusWithdrawnGram Negative Meningitis | Post Traumatic Bacterial MeningitisIsrael
-
Prof. Elizabeth MillerNovartis VaccinesCompletedMeningococcal Meningitis, Serogroup A | Meningococcal Meningitis, Serogroup B | Meningococcal Meningitis, Serogroup C | Meningococcal Meningitis, Serogroup Y | Meningococcal Meningitis, Serogroup WUnited Kingdom
-
Charite University, Berlin, GermanyRecruitingBacterial Meningitis | Implant Infection | Fungal MeningitisGermany
-
Beijing Children's HospitalFirst Affiliated Hospital of Xinjiang Medical University; Xingtai People's... and other collaboratorsUnknownNext Generation Sequencing | Pediatric Bacterial MeningitisChina
-
Kamuzu University of Health SciencesCompletedInfant Bacterial MeningitisMalawi
-
Chiron CorporationUnknownMeningococcal Disease; Meningococcal MeningitisUnited Kingdom
-
Kamuzu University of Health SciencesCompleted
-
Sanofi Pasteur, a Sanofi CompanyCompletedMeningitis | Meningococcal Infections | Meningococcal MeningitisRussian Federation
-
Sanofi Pasteur, a Sanofi CompanyCompletedMeningitis | Meningococcal Infections | Meningococcal MeningitisUnited States, Puerto Rico
Clinical Trials on Mild induced hypothermia (32-34°C)
-
Centre Hospitalier Universitaire de NiceCompleted
-
Danish Procalcitonin Study GroupLundbeck Foundation; TRYG FoundationTerminatedSeptic ShockNetherlands, Denmark, United States
-
Imperial College LondonMedical Research CouncilCompletedHypoxia | Seizures | Asphyxia Neonatorum | EncephalopathyUnited Kingdom
-
Thomas Jefferson UniversityUnknownHypothermia | Cerebral HemorrhageUnited States
-
Lawson Health Research InstituteUniversity of Western Ontario, CanadaUnknownPulseless Electrical Activity | Asystole | Postcardiac ArrestCanada
-
ZOLL Circulation, Inc., USAInstituto de Investigación Hospital Universitario La PazCompletedOut-Of-Hospital Cardiac ArrestGermany, Spain