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Un ensayo de plataforma para infecciones del torrente sanguíneo por gramnegativos (BALANCE+)

5 de noviembre de 2026 actualizado por: Dr. Nick Daneman, Sunnybrook Health Sciences Centre

BALANCE+: una plataforma de ensayo para infecciones del torrente sanguíneo por gramnegativos

BALANCE+ is a perpetual multiple domain randomized controlled platform trial to evaluate various treatment strategies for Gram-negative bloodstream infections (GN BSIs). Each domain addresses critical questions in the management of GN BSIs, aiming to refine treatment strategies, enhance patient outcomes, and reduce antimicrobial resistance.

The initial vanguard pilot RCT (NCT05893147) started on 29 August 2023 and has successfully completed the pilot phase on 24-Apr-2024. All patients enrolled in the vanguard phase are part of the main platform trial.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Descripción detallada

BALANCE+ is an adaptive platform trial evaluating multiple treatment options in patients admitted to the hospital due to Gram negative bloodstream infections (BSIs). It focuses on both cross-cutting and subgroup-specific questions, using an open-label, pragmatic design embedded in routine care.

BALANCE+ addresses the significant health concern of BSIs, which have high morbidity and mortality rates, exacerbated by the global public health threat of antimicrobial resistance (AMR). With rising resistance rates and limited new drug development, effective treatment strategies for BSIs remain under-researched.

BALANCE+ follows the BALANCE trial, which evaluated duration of antibiotic treatment, and aims to further investigate critical questions in managing Gram-negative BSIs. This platform trial will explore various aspects of BSI treatment, including antibiotic de-escalation, oral antibiotic choices, central line management, treatment of specific pathogens, and the necessity of follow-up blood cultures.

BALANCE+ is using Bayesian methods without a fixed sample size. Interim analyses will occur after every 1000th patient in each domain, and then for every 200th patient thereafter. The trial will stop if futility or superiority thresholds are met, or if a domain reaches its ceiling sample size (2500 patients for most domains and 4000 for the beta-lactam versus non-beta-lactam domain) without meeting a stopping threshold.

A vanguard pilot trial involving over 150 patients at 9 hospitals across Canada confirmed the feasibility of the BALANCE+ trial. The main trial will include patients from the vanguard pilot phase since there has been no major change in the overall study design and domains. The adaptive design allows for interim analyses and adjustments by adding or removing domains as per the statistical analysis plan, enhancing the trial's efficiency and relevance.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

2500

Fase

  • No aplica

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Copia de seguridad de contactos de estudio

Ubicaciones de estudio

  • Australia
    • New South Wales
      • Kogarah, New South Wales, Australia, 2217
        • Reclutamiento
        • St George Hospital
        • Investigador principal:
          • Richard Sullivan
        • Contacto:
        • Sub-Investigador:
          • Pam Konecny
        • Contacto:
          • Rachael Roberts, Research Coordinator
      • New Lambton, New South Wales, Australia
        • Reclutamiento
        • John Hunter Hospital
        • Contacto:
        • Contacto:
          • Número de teléfono: +61 2 4921 3000
        • Investigador principal:
          • Joshua Davis
    • Queensland
      • Herston, Queensland, Australia, 4006
        • Reclutamiento
        • Royal Brisbane and Women's Hospital
        • Contacto:
        • Investigador principal:
          • Patrick Harris, Infectious Disease Physician
      • Redcliffe, Queensland, Australia
        • Reclutamiento
        • Redcliffe Hospital
        • Investigador principal:
          • Kevin O'Callaghan
        • Contacto:
      • Sunshine Coast, Queensland, Australia
        • Reclutamiento
        • Sunshine Coast University Hospital
        • Contacto:
        • Investigador principal:
          • Gururaj Nagaraj
    • Victoria
      • Clayton, Victoria, Australia
        • Reclutamiento
        • Monash Medical Center
        • Investigador principal:
          • Ben Rogers
        • Contacto:
    • Western Australia
      • Murdoch, Western Australia, Australia
        • Reclutamiento
        • Fiona Stanley Hospital
        • Contacto:
        • Investigador principal:
          • Edward Raby
      • Murdoch, Western Australia, Australia
        • Reclutamiento
        • St John of God
        • Contacto:
        • Investigador principal:
          • Adrian Regli
  • Canadá
    • Alberta
      • Calgary, Alberta, Canadá
        • Reclutamiento
        • Rockyview General Hospital
        • Investigador principal:
          • Ranjani Somayaji
        • Contacto:
      • Calgary, Alberta, Canadá
        • Reclutamiento
        • Peter Lougheed Centre
        • Investigador principal:
          • Ranjani Somayaji
        • Contacto:
      • Calgary, Alberta, Canadá
        • Reclutamiento
        • South Health Campus
        • Investigador principal:
          • Ranjani Somayaji
        • Contacto:
      • Calgary, Alberta, Canadá
        • Reclutamiento
        • Foothills Hospital
        • Contacto:
          • Ranjani Somayaji, MD
      • Edmonton, Alberta, Canadá
        • Reclutamiento
        • University of Alberta
        • Contacto:
          • Wendy Sligl
          • Número de teléfono: (780) 492-3111
          • Correo electrónico: wsligl@ualberta.ca
        • Investigador principal:
          • Wendy Sligl
    • British Columbia
      • Surrey, British Columbia, Canadá
        • Reclutamiento
        • Surrey Memorial Hospital
        • Investigador principal:
          • Kevin Afra
        • Contacto:
      • Vancouver, British Columbia, Canadá
        • Reclutamiento
        • Vancouver General Hospital
        • Investigador principal:
          • Jennifer Grant
        • Contacto:
    • Manitoba
      • Winnipeg, Manitoba, Canadá
        • Reclutamiento
        • Health Sciences Centre
        • Contacto:
        • Investigador principal:
          • Sylvain Lother
      • Winnipeg, Manitoba, Canadá
        • Reclutamiento
        • St. Boniface Hospital
        • Investigador principal:
          • Terry Wuerz
        • Contacto:
          • Terry Wuerz
          • Número de teléfono: (204) 233-8563
          • Correo electrónico: twuerz@hsc.mb.ca
      • Winnipeg, Manitoba, Canadá
        • Reclutamiento
        • Grace Hospital
        • Contacto:
        • Investigador principal:
          • Gloria Vazquez-Grande
    • New Brunswick
      • Fredericton, New Brunswick, Canadá
        • Reclutamiento
        • Dr. Everett Chalmers Regional Hospital
        • Contacto:
        • Investigador principal:
          • Rosa Rossana
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canadá
        • Reclutamiento
        • Eastern Regional Health Authority
        • Contacto:
          • Peter Daley, MD
    • Ontario
      • Mississauga, Ontario, Canadá
        • Reclutamiento
        • Trillium Health Partners - Mississauga Hospital
        • Contacto:
        • Contacto:
          • Mobina Khurram
        • Investigador principal:
          • Christopher Graham
      • North York, Ontario, Canadá
        • Reclutamiento
        • Humber River Health system
        • Contacto:
          • Ian Brasg
          • Número de teléfono: (416) 242-1000
          • Correo electrónico: ibrasg@hrh.ca
        • Investigador principal:
          • Ian Brasg
      • North York, Ontario, Canadá
        • Reclutamiento
        • North York General Hospital
        • Contacto:
        • Investigador principal:
          • Pavani Das
      • Ottawa, Ontario, Canadá
        • Reclutamiento
        • The Ottawa Hospital
        • Contacto:
          • Derek McFadden, MD
      • St. Catharines, Ontario, Canadá
        • Reclutamiento
        • Niagara Health System
        • Contacto:
          • Aidan Findlater, MD
      • Toronto, Ontario, Canadá
        • Reclutamiento
        • University Health Network
        • Contacto:
          • Bryan Coburn, MD
      • Toronto, Ontario, Canadá, M4N3M5
        • Reclutamiento
        • Sunnybrook Health Sciences Centre
        • Contacto:
        • Contacto:
        • Investigador principal:
          • Rob A Fowler, MD
        • Investigador principal:
          • Nick Daneman, MD
      • Toronto, Ontario, Canadá
        • Reclutamiento
        • Michael Garron Hospital
        • Contacto:
          • Christopher Kandel, MD
      • Toronto, Ontario, Canadá
        • Reclutamiento
        • Mount Sinai Hospital
        • Contacto:
          • Michael Fralick, PhD
      • Toronto, Ontario, Canadá
        • Reclutamiento
        • St. Joseph's Health Centre
        • Contacto:
        • Investigador principal:
          • Kevin Schwartz
    • Quebec
      • Laval, Quebec, Canadá
        • Reclutamiento
        • Hôpital de la Cité de la Santé
        • Contacto:
        • Investigador principal:
          • Marco Bergevin
        • Sub-Investigador:
          • Stéphanie Castonguay
        • Sub-Investigador:
          • Olivier Haeck
        • Sub-Investigador:
          • Esther Simoneau
        • Sub-Investigador:
          • Marios Roussos
        • Sub-Investigador:
          • Natalie Rivest
        • Sub-Investigador:
          • Tuyen Nguyen
      • Laval, Quebec, Canadá
        • Reclutamiento
        • CHU de Québec - Université Laval
        • Contacto:
        • Investigador principal:
          • Francois Lauzier
        • Sub-Investigador:
          • Julie Bestman-Smith
      • Montreal, Quebec, Canadá
        • Reclutamiento
        • Montreal General Hospital- McGill
        • Contacto:
        • Investigador principal:
          • Todd C Lee
        • Investigador principal:
          • Emily Mcdonald
      • Montreal, Quebec, Canadá
        • Reclutamiento
        • Royal Victoria Hospital- McGill
        • Contacto:
        • Investigador principal:
          • Emily McDonald
        • Investigador principal:
          • Todd C Lee
      • Sherbrooke, Quebec, Canadá
        • Reclutamiento
        • Université de Sherbrooke
        • Contacto:
          • François Lamontagne, MD
      • Trois-Rivières, Quebec, Canadá, G8Z 3R9
        • Reclutamiento
        • Centre hospitalier affilié universitaire régional (CHAUR)
        • Contacto:
        • Investigador principal:
          • Jean-François Naud
  • Colombia
    • Cundinamarca
      • Chía, Cundinamarca, Colombia
        • Reclutamiento
        • Universidad de La Sabana
        • Contacto:
        • Investigador principal:
          • Luis Felipe Reyes Velasco
  • Israel
    • Tel Aviv
      • Ramat Gan, Tel Aviv, Israel
        • Reclutamiento
        • Sheba Medical Center
        • Investigador principal:
          • Dafna Yahav
        • Contacto:
  • Nueva Zelanda
    • Auckland
      • Auckland, Auckland, Nueva Zelanda, 2025
        • Reclutamiento
        • Middlemore Hospital
        • Contacto:
        • Contacto:
        • Investigador principal:
          • Susan Morpeth, Clinical Microbiologist
        • Sub-Investigador:
          • Michael Trent Herdman, Specialist Registrar
      • Takapuna, Auckland, Nueva Zelanda, 0622
    • Wellington Region
      • Newtown, Wellington Region, Nueva Zelanda, 6021
        • Reclutamiento
        • Wellington Hospital
        • Contacto:
        • Investigador principal:
          • Maxim Bloomfield
        • Sub-Investigador:
          • Paul Young

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

1 segundo a 130 años (Niño, Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

PLATFORM INCLUSION CRITERIA

Platform Inclusion Criteria:

  • admitted to a participating hospital
  • positive blood culture with Gram negative (GN) bacterium

Platform Exclusion Criteria:

  • patient's goals of care are for palliation with no active treatment
  • moribund patient, not expected to survive > 72 hours
  • previously enrolled in the platform trial
  • not eligible for any domain at the time of screening

DOMAIN SPECIFIC INCLUSION AND EXCLUSION CRITERIA

  1. De-escalation versus no de-escalation domain

    Inclusion Criteria

    - included in BALANCE+ platform

    Exclusion Criteria

    • receiving an empiric antibiotic regimen at the time of blood culture finalization to which the GN pathogen(s) are not sensitive

    • arbapenem-non-susceptible

    • no de-escalation option due to any or all of:

      • antimicrobial resistance
      • allergies
      • medical contraindications
      • drug-drug interaction risk
      • other relevant reason

    • patients with a suspected or proven polymicrobial source of infection

    • > 24 hours since index blood culture susceptibility results finalization

  2. Beta-lactam versus non-beta-lactam oral/enteral treatment domain

    Inclusion Criteria

    • included in BALANCE+ platform
    • initially treated with intravenous antibiotics, but clinical team transitioning patient to oral/enteral antibiotic within 7 days of starting treatment

    Exclusion Criteria

    • enrolled in an arm of another BALANCE+ platform domain which limits the use of oral/enteral therapy:

    • no-de-escalation arm (patients in the no de-escalation arm cannot be randomized into this domain unless they are ready for discharge home, in which case de-escalation is allowable to oral agents at discharge)

    • no non-beta-lactam options due to any or all of:

      • resistance
      • allergies
      • medical contraindications
      • drug-interaction risk
      • other relevant reason

    • no beta-lactam options due to any or all of:

      • resistance
      • allergies
      • medical contraindications
      • drug-interaction risk
      • other relevant reason

    • pregnancy

    • already received >24 hours of oral antibiotics after index blood culture finalization

  3. Central vascular catheter replacement domain

    Inclusion Criteria

    • included in BALANCE+ platform
    • has an indwelling central vascular catheter that was already in place within the 48-hour period before the onset of bloodstream infection (i.e. is not a new catheter placed within 48 hours of the onset of infection)

    Exclusion Criteria

    • patient has no ongoing need for a central vascular catheter

    • patient has definite indication for central vascular catheter removal

    • ongoing septic shock with definite/probable line source o concomitant S. aureus bacteremia

      • concomitant candidemia

    • local suppurative signs (severe redness, warmth, pain, swelling or fluctuance/collection) necessitating catheter removal, or other clinical evidence of infected line (e.g. imaging/echocardiographic findings)

  4. Low-risk AmpC domain

    Inclusion Criteria

    • included in BALANCE+ platform
    • positive blood culture with GN bacterium, of the following species: i. Serratia spp. ii Morganella spp. iii Providencia spp. iv Proteus spp. other than P.mirabilis
    • organism is susceptible to ceftriaxone

    Exclusion Criteria

    - severe allergy to beta-lactams (e.g., type 4 hypersensitivity reaction or DRESS)

    • baseline phenotypic non-susceptiblity to ceftriaxone
    • more than 1 calendar day beyond availability of susceptibility results

  5. Follow up blood culture domain

    Inclusion Criteria

    - included in BALANCE+ platform

    Exclusion Criteria

    • patient died or discharged from hospital prior to day 4
    • blood culture already collected by the treating team at day 4±1
    • >5 days since index positive blood culture collection
    • definite indication for repeat blood culture testing o concomitant S. aureus bacteremia o concomitant Candidemia o clinical suspicion for infective endocarditis

  6. 4 day versus 7-day antibiotic duration

    Inclusion Criteria • improving clinical trajectory, based on meeting all of these criteria by the 4th calendar day of adequate antibiotics:

    o temperature 35.0ºC-37.9ºC

    o not on vasopressors

    o FiO2 ≤ 50%

    Exclusion Criteria

    • Has not undergone successful source control (if required) before completing 4th calendar day of adequate antibiotics

    • Neutropenia (<0.5 × 10⁹/L)

    • solid organ or bone marrow transplantation
    • suspected or documented deep-seated infection requiring prolonged antibiotics

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Desescalada VS No Desescalada
Otro: De-escalation VS No De-escalation

No de-escalation group: continue to receive the same antibiotic that was started initially (as long as it is confirmed to be effective based on the blood culture sensitivity result). De-escalation is only allowed within 7 days if patient is being discharged from hospital.

De-escalation group: switched to narrower spectrum antibiotic (based on spectrum scale specified in protocol).
Comparador activo: Betalactámicos orales VS No betalactámicos orales
Otro: Oral beta-lactams VS non beta-lactams

Beta-lactam antibiotic: This can be, but not limited to, amoxicillin, amoxicillin-clavulanate, cephalexin, cefadroxil, or cefixime.

Non beta-lactam antibiotic: This can be ciprofloxacin, moxifloxacin, levofloxacin or trimethoprim-sulfamethoxazole.
Comparador activo: Retención de catéter vascular central VS Reemplazo de catéter vascular central
Otro: Central vascular catheter retention VS Central vascular catheter replacement

Central vascular catheter replacement: the catheter will be changed by the treating team as soon as possible and within a maximum of 3 calendar days from blood culture finalization (removal must happen within that time; replacement can occur after that time point)

Central vascular catheter retention: the catheter will not be changed and will be retained until it is non functional or no longer needed.
Comparador activo: Cefalosporina VS Carbapenem para organismos AmpC de bajo riesgo
Otro: Cephalosporin VS Carbapenem for low risk AmpC organisms

Cephalosporin (ceftriaxone) at standard doses

Carbapenem (Meropenem or Ertapenem) at standard doses
Comparador activo: Routine follow-up blood culture VS No routine follow-up blood culture

Enrollment to the domain has been completed.
Otro: Routine follow-up blood culture VS No routine follow-up blood culture

Routine follow-up blood culture: routine repeat blood collection 4 days from the index blood collection with positive bacteria.

No follow-up blood culture: no routine repeat blood collection 4 days from the index blood collection with positive bacteria
Comparador activo: 4-day versus 7-day antibiotic duration
Otro: 4-day versus 7- day antibiotic duration

The shorter duration arm will receive 4 days of adequate antibiotics. The longer duration arm will receive 7 days of adequate antibiotics.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Desirability of Outcome Ranking (DOOR) Ordinal Scale which incorporates death, reinfection, readmission, and for some domains incorporates a tie-breaker of new antimicrobial resistance (AMR).
Periodo de tiempo: 90 days

The primary outcome for each domain will use a Desirability of Outcome Ranking (DOOR) ordinal scale in which patients are categorized into the following mutually exclusive categories, ranked from best to worst status:

  1. Alive with no reinfection or readmission.
  2. Alive with reinfection OR readmission.
  3. Alive with reinfection AND readmission.
  4. Dead

For the 4 antibiotic-related domains (the de-escalation versus no de-escalation domain, the beta-lactam versus non-beta-lactam domain, the low risk AmpC domain, and the 4 versus 7 day duration domain) there will be an additional tie-breaker within ordinal levels 1, 2 and 3 based on whether there was new detection of antimicrobial resistance (AMR).
90 days

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Mortalidad a 30 días
Periodo de tiempo: 30 dias
30 dias
Mortalidad a los 90 días
Periodo de tiempo: 90 dias
90 dias
Mortalidad a los 60 días
Periodo de tiempo: 60 días
60 días
Readmisión por todas las causas a los 90 días
Periodo de tiempo: 90 dias
90 dias
Colonización/infección AMR de 90 días
Periodo de tiempo: 90 dias
90 dias
Infección por Clostridioides difficile (CDI) de 90 días
Periodo de tiempo: 90 dias
90 dias
Reinfección de 90 días
Periodo de tiempo: 90 dias
90 dias
Additional Secondary Outcomes for Follow up blood culture domain
Periodo de tiempo: 90 days
  • total duration of antibiotic therapy
  • hospital length of stay
90 days
Additional Secondary Outcomes for De-escalation versus no de-escalation Domain
Periodo de tiempo: 90 days
  • change in total microbiome diversity between the day of randomization and discharge (or day 30 if earlier)
  • net change in resistome AMR burden between the day of randomization and discharge (or day 30 if earlier).
90 days
Additional Secondary Outcomes for Beta-lactam versus non-beta-lactam domain
Periodo de tiempo: 90 days
  • antibiotic-related allergic reaction
  • antibiotic-related adverse event
90 days
Additional Secondary Outcomes for Central vascular catheter replacement versus retention domain
Periodo de tiempo: 90 days
  • pneumothorax or thoracotomy tube insertion related to vascular catheter
  • clinically important bleeding
  • line associated thrombus
  • persistent bacteremia >5d from initial index culture
  • secondary bloodstream infection with new bacterial or fungal organism
90 days
Additional Secondary Outcomes for Low-risk AmpC domain
Periodo de tiempo: 90 days
  • isolation of ESBL producing organism or third generation cephalosporin resistant Gram negative organism
  • isolation of a carbapenem-resistant organism
90 days
Additional domain-specific secondary outcomes in 4-day versus 7-day antibiotic duration
Periodo de tiempo: 90 days

  • antibiotic-related allergic reaction

  • antibiotic-related (non-allergic) adverse event (grade 4+ or 3+ with treatment change)

  • microbiome/resistome sub-study

    • change in total microbiome diversity (Shannon diversity index) between the day of randomization and day 30
    • change in total microbiome diversity (Shannon diversity index) between the day of randomization and day 7
    • net change in resistome AMR burden between the day of randomization and day 30
    • change in total microbiome diversity (Shannon diversity index) between the day of randomization and day 7
90 days

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Sunnybrook Health Sciences Centre

Colaboradores

Canadian Institutes of Health Research (CIHR)
Universidad de la Sabana
Clínica Universidad de La Sabana
Aotearoa Clinical Trials

Investigadores

  • Investigador principal: Nick Daneman, MD, Sunnybrook Health Sciences Centre
  • Investigador principal: Rob Fowler, MD, Sunnybrook Health Sciences Centre

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

24 de abril de 2024

Finalización primaria (Estimado)

1 de abril de 2027

Finalización del estudio (Estimado)

1 de abril de 2028

Fechas de registro del estudio

Enviado por primera vez

25 de julio de 2024

Primero enviado que cumplió con los criterios de control de calidad

31 de julio de 2024

Publicado por primera vez (Actual)

5 de agosto de 2024

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

9 de noviembre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

5 de noviembre de 2026

Última verificación

1 de octubre de 2026

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • 4369-1

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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