Clinical trial NCT03480191: Adjunction of Daptomycin for the Treatment of Pneumococcal Meningitis
Official title: Adjunction of Daptomycin for the Treatment of Pneumococcal Meningitis: AddaMAP Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pneumococcal Meningitis
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2018-03-29
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Pneumococcal meningitis is an infection of the membrane that covers the brain. It is a serious infection which is currently treated with a combination of corticosteroids (dexamethasone) and 3rd generation cephalosporins. Nevertheless, complications associated with meningitis are relatively frequent and severe. Recent animal studies have shown that another antibiotic, daptomycin, can reduce the mortality and long-term effects of pneumococcal meningitis. Daptomycin is widely used worldwide in humans for other diseases, with few side effects.

This study aims to evaluate the effect of daptomycin on the proliferation of the bacterial infection, and therefore on inflammation. Daptomycin will be added to the currently recommended treatment with the same dosage used for other diseases.

Roughly 130 patients with suspected pneumococcal meningitis admitted to the emergency departments of hospitals throughout France will be asked to participate in this study.

The participation period will last approximately 3 months.


Eligibility criteria: Inclusion Criteria:

* Persons aged over 18 years
* With Suspected pneumococcal meningitis :

  * clinical presentation evocative of pneumococcal meningitis : acute onset of ,meningeal signs, history of cranial trauma or fistula, knowledge of alteration of humoral immunity,, asplenia, alcoholism with/or
  * clearly purulent CSF with/ or,
  * presence of diplococcus on the Gram stain of CSF or positive pneumococcal antigen in the CSF, or polymorphonuclear cells in CSF \> 100
* Written consent or inclusion in an emergency
* Affiliation to a social security system

Exclusion Criteria:

* Contraindication to cephalosporin
* Immediate and severe hypersensitivity to β-lactam antimicrobial
* Contraindication to dexamethasone
* Contraindication to daptomycin
* Previous exposition to daptomycin (within one year)
* Women who are able to procreate without effective contraception and pregnant or breastfeeding women
* Patients under ward of court
* Refusal at any time after acceptation of the study from the patient or her/his legal representative.

Primary outcomes:
measure: Disability-free survival, assessed with the modified Rankin Scale (mRS)
timeFrame: At Day 30
Secondary outcomes:
measure: Overall mortality
timeFrame: At Day 30 and Day 90
measure: Disability level assessed with the mRS in surviving patients
timeFrame: At Day 30 and Day 90
measure: Disability level assessed with the Glascow Coma Scale and the Glasgow Outcome Scale in the overall efficacy population
timeFrame: At Day 30 and Day 90
measure: Disability level assessed with mini-mental score in surviving patients
timeFrame: At Day 30 and Day 90
measure: Hearing loss assessed with the Hearing Handicap Inventory test
timeFrame: At Day 30 and Day 90
measure: Hearing loss assessed with audiometry
timeFrame: At Day 30
measure: Hearing loss assessed with the Hearing-it test
timeFrame: At Day 30
measure: Quality of life assessed with the 12-Item Short Form Health Survey (SF-12)
timeFrame: At Day 30 and Day 90
measure: Quality of life assessed with WHO QOL BREF
timeFrame: At Day 30 and Day 90
measure: Number of days without hospitalisation (including ICU)
timeFrame: At Day 30 and Day 90
measure: Number of days without antimicrobial therapy
timeFrame: At Day 30
measure: Frequency and type of side effects related to daptomycine
timeFrame: Within 30 days after daptomycin start
Other outcomes:
Locations:
city: Dijon
country: France
facility: CHU Dijon Bourgogne
Study officials:
References:
citation: Wall EC, Chan JM, Gil E, Heyderman RS. Acute bacterial meningitis. Curr Opin Neurol. 2021 Jun 1;34(3):386-395. doi: 10.1097/WCO.0000000000000934.