Bacterial MeningitisPhase 4IHPOTOTAMNCT00774631
IHPOTOTAM : Induced HyPOthermia TO Treat Adult Meningitis
A Phase 4 study testing Mild induced hypothermia (32-34°C) and local recommendations and guidelines in people with Bacterial Meningitis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacterial Meningitis
- What is being tested?
- Mild induced hypothermia (32-34°C) and local recommendations and guidelines
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2009to Jul 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Bacterial Meningitis
- Being tested
- Mild induced hypothermia (32-34°C), local recommendations and guidelines
- Keywords
- Meningitis, Hypothermia, Intensive care
- Medical subject headings
- Meningitis, Bacterial, Meningitis, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mild induced hypothermia (32-34°C)Procedure or surgery
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 guidelinesProcedure or surgery
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 group | Role | What they receive |
|---|---|---|
| Hypothermia | Experimental | mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming Receives: Procedure: Mild induced hypothermia (32-34°C) |
| No hypothermia | Active comparator | no hypothermia, according to local recommendations and guidelines of medical societies and literature Receives: Procedure: local recommendations and guidelines |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission.
Measured: 3 months
Secondary outcomes (9)
Mortality (assessed on day 14 after admission, day 28, total in-hospital mortality, and at 3 and 6 months)
Measured: 6 months
ICU length of stay
Measured: 6 months
Score on GOS at ICU discharge and 6 months after admission
Measured: 6 months
Neurological examination at discharge and 6 months after admission
Measured: 6 months
Neuropsychological outcome at 6 months in a subset of centres; patient will be tested with a neuropsychological test battery described previously
Measured: 6 months
MRC score on ICU discharge
Measured: 3 months
Prevalence of status EPILEPTISIS
Measured: 6 months
Prevalence of infections (aspiration pneumonia and nosocomial infections)
Measured: 6 months
Potential hypothermia related side effects as cardiac arrhythmia, electrolyte balance, hyperglycemia, bleeding, acute pancreatitis (see definitions further).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2008 (estimated)
- Study startMar 2009
- Primary completionFeb 2012
- Study completionJul 2012
Why it stopped: The sponsor stoppes the study for the security problem.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bacterial MeningitisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- MOURVILLIER Bruno, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00774631
- Sponsor's protocol ID
- P 060217
- Other IDs
- AOM 06 038
- Acronym
- IHPOTOTAM
- Status last verified
- Jul 2012
- First submitted
- 16 Oct 2008
- Last updated
- 17 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
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-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.
PubMed 24105303
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mild Induced Hypothermia to Treat Severe Community Acquired Meningitis in Adults Admitted to Intensive Care Unit
- ClinicalTrials.gov ID
- NCT00774631
- Acronym / sponsor ID
- IHPOTOTAM / P 060217
- Conditions
- Bacterial Meningitis
- Keywords
- Meningitis, Hypothermia, Intensive care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor stoppes the study for the security problem.
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Feb 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 17 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypothermia | Experimental | Procedure: Mild induced hypothermia (32-34°C)mild induced hypothermia (32-34°C) during 48 hours followed by passive rewarming |
| No hypothermia | Active comparator | Procedure: local recommendations and guidelinesno hypothermia, according to local recommendations and guidelines of medical societies and literature |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 or surgery | Hypothermia |
| local recommendations and guidelinesInvestigational 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. | Procedure or surgery | No hypothermia |
Primary outcome
Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission.
Time frame: 3 months
9 secondary outcomes
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
Results and safety
The study was stopped early (reason given: The sponsor stoppes the study for the security problem.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2012.
- Derived from this study: PubMed 24105303Mourvillier 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.
Related trials for Bacterial Meningitis
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
RecruitingObservational study
Fungal Infection Susceptibility
Cryptococcal Infection, Cryptococcal Pneumonia
RecruitingObservational study
Acute Treatment and Long-term Assessment of Adult Infectious Meningitis
Viral Meningitis, Bacterial Meningitis
RecruitingObservational study
Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
Idiopathic CD4+ Lymphocytopenia, Cryptococcal Meningitis
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MOURVILLIER Bruno, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mild induced hypothermia (32-34°C) and local recommendations and guidelines in people with Bacterial Meningitis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The sponsor stoppes the study for the security problem.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with unfavorable outcome (defined as score on Glasgow outcome Scale < 5) at 3 months after admission. (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00774631, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2012.