<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03005145</url>
  </required_header>
  <id_info>
    <org_study_id>0796</org_study_id>
    <nct_id>NCT03005145</nct_id>
  </id_info>
  <brief_title>Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness</brief_title>
  <acronym>BALANCE</acronym>
  <official_title>Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sunnybrook Health Sciences Centre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The World Health Organization, U.S. Centers for Disease Control and Prevention, Association&#xD;
      of Medical Microbiology and Infectious Diseases (AMMI) Canada, and Health Canada have all&#xD;
      declared antimicrobial resistance a global threat to health, based on rapidly increasing&#xD;
      resistance rates and declining new drug development. Up to 30-50% of antibiotic use is&#xD;
      inappropriate, and excessive durations of treatment are the greatest contributor to&#xD;
      inappropriate use. Shorter duration treatment (≤7 days) has been shown in meta-analyses to be&#xD;
      as effective as longer antibiotic treatment for a range of mild to moderate infections. A&#xD;
      landmark trial in critically ill patients with ventilator-associated pneumonia showed that&#xD;
      mortality and relapse rates were non-inferior in patients who received 8 vs 15 days of&#xD;
      treatment. Similar adequately powered randomized trial evidence is lacking for the treatment&#xD;
      of patients with bloodstream infections caused by a wide spectrum of organisms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Bloodstream infections are a common and serious problem, increasing length of hospital stay&#xD;
      by 2-3 weeks, adding $25,000-40,000 in excess hospital costs, and tripling the risk of death.&#xD;
      At the same time, antibiotic overuse is also a common and serious problem, in that 30-50% of&#xD;
      antibiotic use is unnecessary or inappropriate, and results in avoidable drug side effects&#xD;
      such as kidney failure, Clostridioides difficile infection, increased costs, and spiralling&#xD;
      antibiotic resistance rates. The greatest contributor to antibiotic overuse is excessive&#xD;
      durations of treatment.&#xD;
&#xD;
      Extensive research has demonstrated that shorter duration antibiotic treatment (less or equal&#xD;
      to 7 days) is as effective as longer duration treatment for a variety of infectious diseases,&#xD;
      but this question has not been directly studied in the setting of bloodstream infection.&#xD;
      BALANCE team's systematic review of the medical literature, national survey of Canadian&#xD;
      infectious diseases and critical care physicians, multicentre retrospective study and BALANCE&#xD;
      pilot RCT, all support the need for a randomized controlled trial comparing shorter (7 days)&#xD;
      versus longer (14 days) antibiotic therapy for bloodstream infections. Prior to performing&#xD;
      the main trial, Investigators completed a pilot trial in ICU patients to establish the&#xD;
      feasibility of the research design, and to optimize the definitive trial. Investigators also&#xD;
      completed a pilot trial of non-ICUs patients to test the feasibility, compare the patient&#xD;
      population in two settings and to assess the reasonableness of expanding the main BALANCE&#xD;
      Trial to non-ICU wards. The overall recruitment rate of the non-ICU ward pilot RCT exceeded&#xD;
      the recruitment rate in the BALANCE ICU pilot RCT with a protocol adherence of 90%. The&#xD;
      results of this pilot were used to estimate the necessary sample size recalculation, after&#xD;
      merging the BALANCE ward trial with the BALANCE main trial, with the principle of maintaining&#xD;
      an equal to smaller non-inferiority margin by the trial's completion. With the completion of&#xD;
      this pilot RCT, the eligibility criteria for the BALANCE trial are also modified to broaden&#xD;
      the inclusion of all bacteremic patients admitted to hospital. By defining the duration of&#xD;
      treatment for bloodstream infections, BALANCE research program will help maximize the&#xD;
      clinical cure of individual patients, while minimizing their risk of drug side effects, C.&#xD;
      difficile, and antibiotic resistance. Since this intervention would require no new&#xD;
      technology, and would reduce (rather than increase) health care costs, it would offer&#xD;
      immediate benefits to patients and the healthcare system.&#xD;
&#xD;
      The BALANCE RCT will randomize hospitalized patients with bloodstream infection to 7 versus&#xD;
      14 days of adequate antibiotic treatment; the antibiotic drugs, doses, routes and interval&#xD;
      will be left to the discretion of the treating team. Although placebo controls are not&#xD;
      feasible, prolonged allocation concealment to day 7 will be used to mitigate selection bias.&#xD;
      The primary analysis will assess whether 7 days is associated with non-inferior 90 day&#xD;
      survival as compared to 14 days of treatment. Participants from the vanguard BALANCE pilot&#xD;
      RCTs will be included in the BALANCE main RCT, and participating Canadian sites will continue&#xD;
      to enrol patients. BALANCE international collaborators include New Zealand, Australia, Saudi&#xD;
      Arabia, the United States, Israel and Switzerland.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 24, 2017</start_date>
  <completion_date type="Anticipated">August 5, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 5, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>90 day survival</measure>
    <time_frame>90 days from index blood culture</time_frame>
    <description>Survival at 90-days recorded as alive or dead at day 90 following index positive blood culture</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hospital mortality</measure>
    <time_frame>Expected average of 4 weeks assessed upto one year</time_frame>
    <description>Recorded as alive or dead at hospital discharge following index positive blood culture</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU mortality</measure>
    <time_frame>Expected average of 2 weeks assessed upto one year</time_frame>
    <description>Recorded as alive or dead at ICU discharge following index positive blood culture</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse rates of bacteremia with the same organism</measure>
    <time_frame>Upto 30 days after adequate antibiotic treatment</time_frame>
    <description>Defined as the recurrence of bacteremia due to original infecting organism (same Genus and species) after documentation of negative blood cultures or clinical improvement and within 30 days after completing course of adequate antimicrobial therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibiotic allergy and adverse events</measure>
    <time_frame>Upto 30 days from start of antibiotic treatment</time_frame>
    <description>Effect of medication on body that produces the allergic reaction to a medication like:&#xD;
Hives&#xD;
Itching of the skin or eyes&#xD;
Skin rash&#xD;
Swelling of the lips, tongue, or face&#xD;
Wheezing&#xD;
Organ toxicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of C. difficile infection in hospital</measure>
    <time_frame>Upto 30 days after index blood culture collection date</time_frame>
    <description>Defined as a positive PCR or ELISA test for Clostridium difficile toxin in the context of diarrhea within hospital of bacteremia diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of secondary nosocomial infection/colonization with antimicrobial resistant organisms in hospital</measure>
    <time_frame>Upto 30 days after index blood culture collection date</time_frame>
    <description>Colonized or infected with at least one highly-resistant microorganism during their hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>Expected for an average of 30 days assessed up to 1 year</time_frame>
    <description>Defined as the duration between index blood culture and discharge from the ICU for a consecutive 48-hour period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>Expected for an average of 30 days assessed up to 1 year</time_frame>
    <description>Defined as the duration between index blood culture and discharge date from hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical ventilation duration</measure>
    <time_frame>Expected for an average of 30 days</time_frame>
    <description>Defined as the number of consecutive days receiving invasive (via an endotracheal tube or tracheostomy), or non-invasive (via a facemask, nasal mask, or helmet) ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibiotic free days</measure>
    <time_frame>Upto 30 days after adequate antibiotic treatment</time_frame>
    <description>Defined as the number of days during the 28 days after the start of adequate antibiotics in which patients did not receive any antibiotics.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3622</enrollment>
  <condition>Bacteremia</condition>
  <condition>Intensive Care</condition>
  <condition>Critically Ill</condition>
  <condition>Sepsis</condition>
  <condition>Mortality</condition>
  <condition>Antimicrobial</condition>
  <arm_group>
    <arm_group_label>Short duration (7 days)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in 7 day arm will receive adequate antibiotics until the end of day 7 only</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Long duration (14 days)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in 14 day arm will receive adequate antibiotics until the end of day 14 only</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>7 days of adequate antibiotic treatment</intervention_name>
    <description>The choice of treatment including type, dose, route and interval of antibiotic will be left at the discretion of treating team as long as it is appropriate for the bacteremia</description>
    <arm_group_label>Short duration (7 days)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>14 days of adequate antibiotic treatment.</intervention_name>
    <description>The choice of treatment including type, dose, route and interval of antibiotic will be left at the discretion of treating team as long as it is appropriate for the bacteremia</description>
    <arm_group_label>Long duration (14 days)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient is in ICU or non-ICU ward at the time the blood culture is drawn or reported&#xD;
             as positive.&#xD;
&#xD;
          2. Patient has a positive blood culture with pathogenic bacteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient already enrolled in the trial&#xD;
&#xD;
          2. Patient has severe immune system compromise, as defined by: absolute neutrophil count&#xD;
             &lt;0.5x109/L; or is receiving immunosuppressive treatment for solid organ or bone marrow&#xD;
             or stem cell transplant&#xD;
&#xD;
          3. Patient has a prosthetic heart valve or synthetic endovascular graft (post major&#xD;
             vessel repair with synthetic material) (note: coronary artery stents are not an&#xD;
             exclusion)&#xD;
&#xD;
          4. Patient has documented or suspected syndrome with well-defined requirement for&#xD;
             prolonged treatment:&#xD;
&#xD;
             i) infective endocarditis; ii) osteomyelitis/septic arthritis; iii)&#xD;
             undrainable/undrained abscess; iv) unremovable/unremoved prosthetic-associated&#xD;
             infection (e.g. infected pacemaker, prosthetic joint infection, ventriculoperitoneal&#xD;
             shunt infection etc.) (note: central venous catheters, including tunneled central&#xD;
             intravenous catheter, and urinary catheters are not excluded unless the treating&#xD;
             clinical team does not have equipoise for enrollment and randomization to either&#xD;
             group)&#xD;
&#xD;
          5. Patient has a single positive blood culture with a common contaminant organism&#xD;
             according to Clinical Laboratory &amp; Standards Institute (CLSI) Guidelines: coagulase&#xD;
             negative staphylococci; or Bacillus spp.; or Corynebacterium spp.; or&#xD;
             Propionobacterium spp.; or Aerococcus spp.; or Micrococcus spp.&#xD;
&#xD;
          6. Patient has a positive blood culture with Staphylococcus aureus or Staphylococcus&#xD;
             lugdunensis&#xD;
&#xD;
          7. Patient has a positive blood culture with Candida spp. or other fungal species.&#xD;
&#xD;
          8. Blood culture grows rare bacterial pathogens requiring prolonged treatment (e.g.&#xD;
             Mycobacteria spp., Nocardia spp., Actinomyces spp., Brucella spp., Burkholderia&#xD;
             pseudomallei)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nick Daneman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Health Sciences Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NYU School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bankstown Hospital</name>
      <address>
        <city>Bankstown</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. George Hospital</name>
      <address>
        <city>Kogarah</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hunter Hospital</name>
      <address>
        <city>New Lambton Heights</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wollongong Hospital ICU</name>
      <address>
        <city>Wollongong</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunshine Coast University Hospital</name>
      <address>
        <city>Birtinya</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ballarat Hospital</name>
      <address>
        <city>Ballarat</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bendigo Hospital</name>
      <address>
        <city>Bendigo</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Casey Hospital</name>
      <address>
        <city>Berwick</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Medical Centre</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dandenong Hospital- Monash Health</name>
      <address>
        <city>Dandenong</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Frankston Hospital</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peninsula Private Hospital</name>
      <address>
        <city>Langwarrin</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cabrini Health</name>
      <address>
        <city>Malvern</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fiona Stanley Hospital</name>
      <address>
        <city>Murdoch</city>
        <state>Western Australia</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John of God Hospital</name>
      <address>
        <city>Subiaco</city>
        <state>Western Australia</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Foothills Hospital</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peter Lougheed Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lions Gate Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Columbian Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Paul's Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver General Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver Island Health</name>
      <address>
        <city>Victoria</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Manitoba</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastern Regional Health Authority</name>
      <address>
        <city>Saint John's</city>
        <state>Newfoundland and Labrador</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth II Hospital</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William Osler Health System</name>
      <address>
        <city>Brampton</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brantford General Hospital</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamilton General Hospital</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph's Healthcare</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kingston General Hospital</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trillium Health Partners</name>
      <address>
        <city>Mississauga</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Niagara Health System</name>
      <address>
        <city>St. Catharines</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Sciences North</name>
      <address>
        <city>Sudbury</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michael Garron Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North York General Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph's Health Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Michael's Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto General Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Western Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier de l'Université de Montréal (CHUM)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Maisonneuve-Rosemont</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospitalier Régional de Trois-Rivières</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montreal General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut universitaire de cardiologie et de pneumologie de Québec</name>
      <address>
        <city>Québec</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Victoria Hospital</name>
      <address>
        <city>Québec</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Université de Sherbrooke</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier affilié universitaire de Québec</name>
      <address>
        <city>Quebec</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petah Tikva</city>
        <state>Tel Aviv</state>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheba Medical Center</name>
      <address>
        <city>Tel HaShomer</city>
        <state>Tel Aviv</state>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland City Hospital</name>
      <address>
        <city>Auckland</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Middlemore Hospital</name>
      <address>
        <city>Auckland</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christchurch Hospital</name>
      <address>
        <city>Christchurch</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waikato Hospital</name>
      <address>
        <city>Hamilton</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taranaki Hospital</name>
      <address>
        <city>New Plymouth</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rotorua Hospital</name>
      <address>
        <city>Rotorua</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellington Hospital</name>
      <address>
        <city>Wellington</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Faisal Specialist Hospital &amp; Research Centre</name>
      <address>
        <city>Jeddah</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Abdulaziz Medical City</name>
      <address>
        <city>Riyadh</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University hospital Bern</name>
      <address>
        <city>Bern</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>Israel</country>
    <country>New Zealand</country>
    <country>Saudi Arabia</country>
    <country>Switzerland</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>May 18, 2023</last_update_submitted>
  <last_update_submitted_qc>May 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bacteremia</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Antibiotics, Antitubercular</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03005145
org study id: 0796
nct id: NCT03005145
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The World Health Organization, U.S. Centers for Disease Control and Prevention, Association
      of Medical Microbiology and Infectious Diseases (AMMI) Canada, and Health Canada have all
      declared antimicrobial resistance a global threat to health, based on rapidly increasing
      resistance rates and declining new drug development. Up to 30-50% of antibiotic use is
      inappropriate, and excessive durations of treatment are the greatest contributor to
      inappropriate use. Shorter duration treatment (≤7 days) has been shown in meta-analyses to be
      as effective as longer antibiotic treatment for a range of mild to moderate infections. A
      landmark trial in critically ill patients with ventilator-associated pneumonia showed that
      mortality and relapse rates were non-inferior in patients who received 8 vs 15 days of
      treatment. Similar adequately powered randomized trial evidence is lacking for the treatment
      of patients with bloodstream infections caused by a wide spectrum of organisms.
Bloodstream infections are a common and serious problem, increasing length of hospital stay
      by 2-3 weeks, adding $25,000-40,000 in excess hospital costs, and tripling the risk of death.
      At the same time, antibiotic overuse is also a common and serious problem, in that 30-50% of
      antibiotic use is unnecessary or inappropriate, and results in avoidable drug side effects
      such as kidney failure, Clostridioides difficile infection, increased costs, and spiralling
      antibiotic resistance rates. The greatest contributor to antibiotic overuse is excessive
      durations of treatment.

      Extensive research has demonstrated that shorter duration antibiotic treatment (less or equal
      to 7 days) is as effective as longer duration treatment for a variety of infectious diseases,
      but this question has not been directly studied in the setting of bloodstream infection.
      BALANCE team's systematic review of the medical literature, national survey of Canadian
      infectious diseases and critical care physicians, multicentre retrospective study and BALANCE
      pilot RCT, all support the need for a randomized controlled trial comparing shorter (7 days)
      versus longer (14 days) antibiotic therapy for bloodstream infections. Prior to performing
      the main trial, Investigators completed a pilot trial in ICU patients to establish the
      feasibility of the research design, and to optimize the definitive trial. Investigators also
      completed a pilot trial of non-ICUs patients to test the feasibility, compare the patient
      population in two settings and to assess the reasonableness of expanding the main BALANCE
      Trial to non-ICU wards. The overall recruitment rate of the non-ICU ward pilot RCT exceeded
      the recruitment rate in the BALANCE ICU pilot RCT with a protocol adherence of 90%. The
      results of this pilot were used to estimate the necessary sample size recalculation, after
      merging the BALANCE ward trial with the BALANCE main trial, with the principle of maintaining
      an equal to smaller non-inferiority margin by the trial's completion. With the completion of
      this pilot RCT, the eligibility criteria for the BALANCE trial are also modified to broaden
      the inclusion of all bacteremic patients admitted to hospital. By defining the duration of
      treatment for bloodstream infections, BALANCE research program will help maximize the
      clinical cure of individual patients, while minimizing their risk of drug side effects, C.
      difficile, and antibiotic resistance. Since this intervention would require no new
      technology, and would reduce (rather than increase) health care costs, it would offer
      immediate benefits to patients and the healthcare system.

      The BALANCE RCT will randomize hospitalized patients with bloodstream infection to 7 versus
      14 days of adequate antibiotic treatment; the antibiotic drugs, doses, routes and interval
      will be left to the discretion of the treating team. Although placebo controls are not
      feasible, prolonged allocation concealment to day 7 will be used to mitigate selection bias.
      The primary analysis will assess whether 7 days is associated with non-inferior 90 day
      survival as compared to 14 days of treatment. Participants from the vanguard BALANCE pilot
      RCTs will be included in the BALANCE main RCT, and participating Canadian sites will continue
      to enrol patients. BALANCE international collaborators include New Zealand, Australia, Saudi
      Arabia, the United States, Israel and Switzerland.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 90 day survival
time frame: 90 days from index blood culture
description: Survival at 90-days recorded as alive or dead at day 90 following index positive blood culture
measure: Hospital mortality
time frame: Expected average of 4 weeks assessed upto one year
description: Recorded as alive or dead at hospital discharge following index positive blood culture
measure: ICU mortality
time frame: Expected average of 2 weeks assessed upto one year
description: Recorded as alive or dead at ICU discharge following index positive blood culture
measure: Relapse rates of bacteremia with the same organism
time frame: Upto 30 days after adequate antibiotic treatment
description: Defined as the recurrence of bacteremia due to original infecting organism (same Genus and species) after documentation of negative blood cultures or clinical improvement and within 30 days after completing course of adequate antimicrobial therapy.
measure: Antibiotic allergy and adverse events
time frame: Upto 30 days from start of antibiotic treatment
description: Effect of medication on body that produces the allergic reaction to a medication like:
Hives
Itching of the skin or eyes
Skin rash
Swelling of the lips, tongue, or face
Wheezing
Organ toxicity
measure: Rates of C. difficile infection in hospital
time frame: Upto 30 days after index blood culture collection date
description: Defined as a positive PCR or ELISA test for Clostridium difficile toxin in the context of diarrhea within hospital of bacteremia diagnosis.
measure: Rates of secondary nosocomial infection/colonization with antimicrobial resistant organisms in hospital
time frame: Upto 30 days after index blood culture collection date
description: Colonized or infected with at least one highly-resistant microorganism during their hospital stay
measure: ICU length of stay
time frame: Expected for an average of 30 days assessed up to 1 year
description: Defined as the duration between index blood culture and discharge from the ICU for a consecutive 48-hour period
measure: Hospital length of stay
time frame: Expected for an average of 30 days assessed up to 1 year
description: Defined as the duration between index blood culture and discharge date from hospital
measure: Mechanical ventilation duration
time frame: Expected for an average of 30 days
description: Defined as the number of consecutive days receiving invasive (via an endotracheal tube or tracheostomy), or non-invasive (via a facemask, nasal mask, or helmet) ventilation
measure: Antibiotic free days
time frame: Upto 30 days after adequate antibiotic treatment
description: Defined as the number of days during the 28 days after the start of adequate antibiotics in which patients did not receive any antibiotics.
arm group label: Short duration (7 days)
arm group type: Active Comparator
description: Patients in 7 day arm will receive adequate antibiotics until the end of day 7 only
arm group label: Long duration (14 days)
arm group type: Active Comparator
description: Patients in 14 day arm will receive adequate antibiotics until the end of day 14 only
intervention type: Other
intervention name: 7 days of adequate antibiotic treatment
description: The choice of treatment including type, dose, route and interval of antibiotic will be left at the discretion of treating team as long as it is appropriate for the bacteremia
arm group label: Short duration (7 days)
intervention type: Other
intervention name: 14 days of adequate antibiotic treatment.
description: The choice of treatment including type, dose, route and interval of antibiotic will be left at the discretion of treating team as long as it is appropriate for the bacteremia
arm group label: Long duration (14 days)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nick Daneman, MD
role: Principal Investigator
affiliation: Sunnybrook Health Sciences Centre
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country: Australia
country: Canada
country: Israel
country: New Zealand
country: Saudi Arabia
country: Switzerland
country: United States
responsible party type: Sponsor
mesh term: Bacteremia
mesh term: Critical Illness
mesh term: Anti-Bacterial Agents
mesh term: Antibiotics, Antitubercular
sharing ipd: No