Combating Multidrug-resistant Gram-negative Bacteria in Africa Through Diagnostic and Antimicrobial Stewardship (ComBac)
Combating Multidrug-Resistant Gram-Negative Bacteria in Africa Through Diagnostic and Antimicrobial Stewardship: A Multicentre, Prospective Quasi-experimental Two-stage Study
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
A multicentric, prospective, quasi-experimental study, consisting of two stages, i.e. one observational stage and one interventional stage. The study will be conducted in a total of six hospitals in three countries: Côte d'Ivoire, Guinea-Bissau and Nigeria.
During the preparatory phase of this study and before the observational study stage 1 starts, blood culture diagnostics and indications for microbiological sampling will be harmonized across all sites and site feasibility assessments will be conducted.
Study stage 1: Antimicrobial susceptibility data of all GNB BSI and detailed assessment of the epidemiology, antimicrobial susceptibility and clinical outcome of MDR GNB in patients with BSIs and their clinical evolution following the standard of care at the individual sites will be collected. Duration: 12 months.
Algorithm development: Based on data obtained during stage 1, setting-tailored diagnosis-treatment algorithms that provide guidance on and access to novel antibiotics will be developed. Duration: ≤6 months
Study stage 2: Implementation of the clinical diagnosis-treatment algorithm in routine clinical care through AMS teams and evaluation of the effects of the algorithm implementation on mortality, the clinical outcome and microbiological cure. Duration: 12 months.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Sören L Becker, Prof. Dr. Dr.
- Número de teléfono: +4968411623900
- Correo electrónico: soeren.becker@uks.eu
Copia de seguridad de contactos de estudio
- Nombre: Jacqueline Rehner, Dr.
- Número de teléfono: +4915754996344
- Correo electrónico: Jacqueline.Rehner@uks.eu
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
Patient with detection of a presumed multidrug-resistant Gram-negative bacterium (MDR GNB), identified by growth on MDR screening agar, in ≥1 blood culture bottle.
Provision of written informed consent by the patient or the patient's parent(s)/legal representative(s).
Exclusion Criteria:
- Patients with negative blood culture or with detection of Gram-positive bacteria or mycobacteria or fungi in blood culture
Patients with GNB in blood culture that are not resistant to third-generation cephalosporins (ceftriaxone or cefotaxim) or carbapenems (meropenem)
Patients with polymicrobial infection
Patients with GNB detected in blood cultures and without systemic infection signs, in whom the microbiological finding is unambiguously interpreted as contamination not necessitating antimicrobial treatment
Patient already recruited for concurrent participation in other clinical studies or trials
Patients with known anaphylactic reactions or severe hypersensitivity to beta-lactam antibiotics
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Diagnóstico
- Asignación: N / A
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Otro: Treatment according to AMS algorithm
There is no real separation into arms.
Everyone will receive the applicable treatment.
It is quasi-experimental.
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In this study stage, a diagnosis-treatment algorithm that will have been developed based on data collected during study stage 1, will be employed as the intervention to guide the choice of antibiotics active against MDR GNB BSIs.
Coupled to the algorithm, a set of specific antibiotics will be made available in the different study settings for treatment of patients with infections due to MDR GNB, for which no equally effective antibiotics are routinely available in the study countries.
Previously held discussions with the regulatory agencies in the study countries will feed into the development of the algorithm.
The novel treatment options include antibiotics which retain activity in MDR GNB with specific resistance profiles such as ESBL-producing isolates and those with carbapenem resistance.
If an antibiotic is not yet licensed in the study country, its use will follow the European Medicines Agency's (EMA) licensing recommendations.
The following drugs will be used whenever the causa
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Clinical cure
Periodo de tiempo: 14 days
|
All cause mortality after 14 days after treatment initiation Stage 1 versus Stage 2.
|
14 days
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Secondary outcomes
Periodo de tiempo: 28 days
|
Stage 1 versus Stage 2 Clinical cure Description: Proportion of participants achieving clinical cure within 7 days of inclusion, defined as resolution or significant improvement of signs and symptoms of infection (e.g., fever, hemodynamic instability, organ dysfunction), based on the judgement of the treating physician and, where applicable, the antimicrobial stewardship (AMS) team using a standardized clinical assessment sheet in conjunction with laboratory parameters. Time Frame: Within 7 days after inclusion |
28 days
|
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Secondary outcomes
Periodo de tiempo: 28 days
|
Stage 1 versus Stage 2 for all mentioned below: All-cause mortality Description: Proportion of participants who die from any cause within 28 days after inclusion. Time Frame: Day 28 |
28 days
|
|
Secondary outcomes
Periodo de tiempo: 28 days
|
Stage 1 versus Stage 2 Microbiological cure Description: Proportion of participants achieving clearance of bloodstream infection, defined as at least one negative pair of blood culture bottles drawn ≥48 hours after treatment initiation and no subsequent positive blood culture with the same pathogen identified. Time Frame: Up to Day 28 |
28 days
|
|
Secondary outcomes
Periodo de tiempo: 28 days
|
Adherence to the clinical algorithm Description: Proportion of treatment decisions in Stage 2 that are consistent with the study clinical algorithm. Time Frame: During antimicrobial treatment, up to Day 28 |
28 days
|
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Secondary outcomes
Periodo de tiempo: 28 days
|
Appropriateness of antimicrobial therapy Description: Proportion of participants receiving antimicrobial therapy deemed appropriate according to pathogen susceptibility results and study treatment guidelines. Time Frame: Up to Day 28 |
28 days
|
|
Secondary outcomes
Periodo de tiempo: 28 days
|
MDR pathogen-specific mortality Description: Proportion of participants with bloodstream infection caused by multidrug-resistant Gram-negative bacteria who die within 28 days. Time Frame: Day 28 |
28 days
|
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Secondary outcomes
Periodo de tiempo: 28 days
|
Adverse event profile of study antimicrobials Description: Incidence and severity of adverse events associated with meropenem, ceftazidime-avibactam, cefiderocol, and ceftazidime-avibactam plus aztreonam, as applicable. Time Frame: Up to Day 28 |
28 days
|
|
Secondary outcomes
Periodo de tiempo: 28 days
|
Clonality of MDR Gram-negative bloodstream isolates Description: Genetic relatedness of multidrug-resistant Gram-negative bacterial strains isolated from bloodstream infections at participating hospitals, assessed by molecular typing methods. Time Frame: During study period and analysis of collected isolates |
28 days
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Aaron O Aboderin, Prof. Dr., Obafemi Awolowo University Nigeria
Publicaciones y enlaces útiles
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- ComBac-AfricaClinicalTrial
- Project 101190791 (Otro identificador: EDCTP3)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
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