Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study
Background The leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive host response to the pneumococcal lysis. Experimental in vitro and in vivo data sho...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-07-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/13/7/e073032.full |
| _version_ | 1827172293404524544 |
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| author | Lionel Piroth Mathieu Blot Pascal Chavanet Christine Binquet Isabelle Fournel Abderrahmane Bourredjem Thibault Sixt |
| author_facet | Lionel Piroth Mathieu Blot Pascal Chavanet Christine Binquet Isabelle Fournel Abderrahmane Bourredjem Thibault Sixt |
| author_sort | Lionel Piroth |
| collection | DOAJ |
| description | Background The leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive host response to the pneumococcal lysis. Experimental in vitro and in vivo data show that the combination of corticosteroids/third-generation cephalosporins and the non-lytic antibiotic, daptomycin, has synergistic effects with (1) a rapid cerebrospinal fluid sterilisation, (2) less brain damages and (3) less loss of cognitive performances. Despite these encouraging results, daptomycin has never been evaluated in adult patients with pneumococcal meningitis.Methods and analysis The AddaMAP trial is a phase II, open-label, Simon’s two-stage, multicentre trial that has been designed to assess the efficacy and safety of adding daptomycin (10 mg/kg/d for 8 days) to the recommended treatment (corticosteroids+third generation cephalosporin) in adults with confirmed pneumococcal meningitis. The main endpoint is the disability-free survival (defined as modified Rankin Scale mRS≤2) at day 30. Secondary outcomes are overall mortality, disability at D30 and D90 (mRS, Glasgow Coma Scale and Glasgow Outcome Scales, mini-mental score), hearing loss (Hearing Handicap Inventory Test at D30 and D90, routine audiometric test and Hearing-it test at D30), and quality of life (12-item Short Form Survey and WHO QOL BREF). Seventy-two analysable patients are required.Ethics and dissemination The study protocol was approved by the Institutional Review Board of the IDF 1 of the ethics committee on 16 January 2018, and authorisation was obtained from the Agence Nationale de Securité des Médicaments et des Produits de Santé on 22 September 2017. The results will be submitted for publication in a peer-reviewed journal.Trial registration number NCT03480191. |
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| format | Article |
| id | doaj.art-4716665870cd4c7f92733d86c6899760 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2025-03-21T03:21:27Z |
| publishDate | 2023-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-4716665870cd4c7f92733d86c68997602024-08-01T07:30:09ZengBMJ Publishing GroupBMJ Open2044-60552023-07-0113710.1136/bmjopen-2023-073032Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP studyLionel Piroth0Mathieu Blot1Pascal Chavanet2Christine Binquet3Isabelle Fournel4Abderrahmane Bourredjem5Thibault Sixt6Infectious Diseases Department, University Hospital Centre Dijon Bourgogne, Dijon, FranceInfectious Diseases Department, University Hospital, Dijon, FranceInfectious Diseases Department, University Hospital, Dijon, FranceINSERM, CIC 1432, Module Epidémiologie Clinique, Dijon, FranceINSERM, CIC 1432, Module Epidémiologie Clinique, Dijon, FranceINSERM, CIC 1432, Module Epidémiologie Clinique, Dijon, FranceInfectious Diseases Department, University Hospital, Dijon, FranceBackground The leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive host response to the pneumococcal lysis. Experimental in vitro and in vivo data show that the combination of corticosteroids/third-generation cephalosporins and the non-lytic antibiotic, daptomycin, has synergistic effects with (1) a rapid cerebrospinal fluid sterilisation, (2) less brain damages and (3) less loss of cognitive performances. Despite these encouraging results, daptomycin has never been evaluated in adult patients with pneumococcal meningitis.Methods and analysis The AddaMAP trial is a phase II, open-label, Simon’s two-stage, multicentre trial that has been designed to assess the efficacy and safety of adding daptomycin (10 mg/kg/d for 8 days) to the recommended treatment (corticosteroids+third generation cephalosporin) in adults with confirmed pneumococcal meningitis. The main endpoint is the disability-free survival (defined as modified Rankin Scale mRS≤2) at day 30. Secondary outcomes are overall mortality, disability at D30 and D90 (mRS, Glasgow Coma Scale and Glasgow Outcome Scales, mini-mental score), hearing loss (Hearing Handicap Inventory Test at D30 and D90, routine audiometric test and Hearing-it test at D30), and quality of life (12-item Short Form Survey and WHO QOL BREF). Seventy-two analysable patients are required.Ethics and dissemination The study protocol was approved by the Institutional Review Board of the IDF 1 of the ethics committee on 16 January 2018, and authorisation was obtained from the Agence Nationale de Securité des Médicaments et des Produits de Santé on 22 September 2017. The results will be submitted for publication in a peer-reviewed journal.Trial registration number NCT03480191.https://bmjopen.bmj.com/content/13/7/e073032.full |
| spellingShingle | Lionel Piroth Mathieu Blot Pascal Chavanet Christine Binquet Isabelle Fournel Abderrahmane Bourredjem Thibault Sixt Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study BMJ Open |
| title | Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study |
| title_full | Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study |
| title_fullStr | Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study |
| title_full_unstemmed | Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study |
| title_short | Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study |
| title_sort | addition of daptomycin for the treatment of pneumococcal meningitis protocol for the addamap study |
| url | https://bmjopen.bmj.com/content/13/7/e073032.full |
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