{
  "abstract": "Objectives Gram negative bloodstream infections (GN BSI) are a leading cause of mortality worldwide, and antibiotic treatment approaches remain understudied. BALANCE+ is a perpetual Bayesian adaptive platform trial to test multiple treatment questions for hospitalised patients with GN BSI. The vanguard phase objective was to test the feasibility of the main trial.Design Adaptive platform trial with five initial domains of investigation, each with open label 1:1 randomisation.Setting Ten hospitals across four Canadian provinces.Participants Individuals admitted to hospital with blood cultures yielding Gram negative bacteria.Interventions The five initial domains of investigation included: antibiotic de-escalation versus no de-escalation; oral transition to beta-lactam versus non-beta-lactam treatment; routine versus no routine follow-up blood cultures (FUBCs); central vascular catheter replacement versus retention; and, ceftriaxone versus carbapenem treatment for low risk AmpC organisms.Primary outcome measures Domain-specific recruitment rates and protocol adherence.Results During the vanguard phase, 719 patients were screened, of whom 563 (78.3%) were eligible, with 179 (31.8%) enrolled into the platform. The platform recruitment rate was 1.37 patients/site-week. Recruitment varied by domain: routine versus no FUBC domain 1.23 patients/site-week; oral beta-lactam versus non-beta-lactam domain 0.48; de-escalation versus no de-escalation domain 0.28; low risk AmpC domain 0.02; catheter replacement versus retention domain 0.01. Domain specific protocol adherence rates were 145/158 (91.8%) for routine versus no routine FUBC, 53/60 (88.3%) for oral beta-lactam versus non-beta-lactam, 26/33 (78.8%) for de-escalation versus no de-escalation, 3/3 (100%) for low risk AmpC, and 0/1 (0%) for line replacement versus retention. There was complete ascertainment of all study outcomes in hospital 170/170 (100%) and near complete ascertainment at 90 days 162/170 (95.3%).Conclusions The vanguard phase demonstrated overall trial feasibility by recruitment rate and protocol adherence, with differences across interventions, leading to a transition to the main BALANCE+ platform trial with minimal protocol modifications.Trial registration number NCT05893147.",
  "authors": [
    {
      "affiliations": [
        "Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Nick Daneman"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Sinai Health/University Health Network, Department of Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Jennie Johnstone"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada"
      ],
      "name": "Todd C Lee"
    },
    {
      "affiliations": [
        "Department of Medicine, University of Ottawa, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Derek R MacFadden"
    },
    {
      "affiliations": [
        "Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada"
      ],
      "name": "Emily G McDonald"
    },
    {
      "affiliations": [
        "Department of Microbiology and Infectious Diseases, Middlemore Hospital, University of Auckland, Auckland, New Zealand"
      ],
      "name": "Susan C Morpeth"
    },
    {
      "affiliations": [
        "Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Sean W X Ong"
    },
    {
      "affiliations": [
        "ADVANCE-ID, Saw Swee Hock School of Public Health, National University of Singapore, Singapore"
      ],
      "name": "David L Paterson"
    },
    {
      "affiliations": [
        "Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Ruxandra L Pinto"
    },
    {
      "affiliations": [
        "Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Asgar Rishu"
    },
    {
      "affiliations": [
        "Centre for Inflammatory Diseases, Monash University School of Clinical Sciences at Monash Health, Clayton, Victoria, Australia"
      ],
      "name": "Benjamin A Rogers"
    },
    {
      "affiliations": [
        "Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel",
        "Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan, Israel"
      ],
      "name": "Dafna Yahav"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, University Health Network, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Bryan Coburn"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Memorial University, Newfoundland, Newfoundland, Canada"
      ],
      "name": "Peter Daley"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, North York General Hospital, Toronto, Ontario, Canada"
      ],
      "name": "Pavani Das"
    },
    {
      "affiliations": [
        "Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada"
      ],
      "name": "Kirsten Fiest"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Niagara Health, St. Catharines, Ontario, Canada"
      ],
      "name": "Aidan Findlater"
    },
    {
      "affiliations": [
        "Division of General Internal Medicine, Sinai Health, Toronto, Ontario, Canada"
      ],
      "name": "Mike Fralick"
    },
    {
      "affiliations": [
        "Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Mithun George"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Michael Garron Hospital, Toronto, Ontario, Canada"
      ],
      "name": "Christopher Kandel"
    },
    {
      "affiliations": [
        "Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada"
      ],
      "name": "Archana Malavade"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Michael Garron Hospital, Toronto, Ontario, Canada"
      ],
      "name": "Jeff Powis"
    },
    {
      "affiliations": [
        "Division of Infectious Diseases, Department of Medicine, University of Calgary, Calgary, Alberta, Canada"
      ],
      "name": "Ranjani Somayaji"
    },
    {
      "affiliations": [
        "Department of Medicine and Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Robert Fowler"
    },
    {
      "affiliations": [],
      "name": "The BALANCE+ Investigators, and the Association of Medical Microbiology and Infectious Disease Canada Clinical Research Network and the Canadian Critical Care Trials Group"
    }
  ],
  "title": "Assessing the feasibility of a platform trial for Gram negative bloodstream infections: results from the vanguard phase of BALANCE+",
  "uid": "f9e65869-ca1e-567d-b68a-890a939e5e0e"
}