<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/NCT02987790</url>
  </required_header>
  <id_info>
    <org_study_id>PCRxBestPractice</org_study_id>
    <nct_id>NCT02987790</nct_id>
  </id_info>
  <brief_title>Duration of Antibiotic Therapy in Critically Ill Patients: C-reactive Protein-guided Therapy Versus Best Practice</brief_title>
  <official_title>Duration of Antibiotic Therapy in Critically Ill Patients: C-reactive Protein-guided Therapy Versus Best Practice</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federal University of Minas Gerais</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundação de Amparo à Pesquisa do estado de Minas Gerais</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Federal University of Minas Gerais</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The judicious use of antibiotics is one of the main measures to limit the emergence of&#xD;
      multidrug-resistant pathogen related to excessive antimicrobial use. A recent study&#xD;
      demonstrated that C-reactive protein (CRP) was as useful as procalcitonin (PCT) in reducing&#xD;
      the time of antibiotic therapy in adult septic patients treated in the ICU setting.&#xD;
      Therefore, the present study proposes to compare the time of use of antimicrobials, costs of&#xD;
      hospitalization and clinical outcomes of interest among a group of antibiotic therapy guided&#xD;
      by serum levels of CRP and a group of therapy based on the best practices of antibiotic&#xD;
      therapy (Best Practice).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All adult patients (aged&gt; 17 years), hospitalized at the ICU (total of 50 beds) of the&#xD;
      Hospital das Clínicas - UFMG, with an assumed or proven infection, will be considered for&#xD;
      inclusion. Patients who meet the inclusion and exclusion criteria will be allocated randomly&#xD;
      into one of the following groups: 1) PCR group: antibiotic therapy will be discontinued&#xD;
      according to serum CRP levels; 2) &quot;Best Practice&quot; group, length of antibiotic therapy based&#xD;
      on the most recent guidelines in the medical literature, according to the focus and / or&#xD;
      causative micro-organism. PCR assays shall be performed daily on serum obtained from blood&#xD;
      collected for routine intensive care examinations up to 2 days after antibiotic withdrawal.&#xD;
      In the PCR group, antibiotic suspension will be encouraged when levels of this marker are&#xD;
      &lt;35mg / L (if peak PCR below 100mg / L); or reduce 50% of the highest value (if PCR peak &gt;&#xD;
      100mg / L), with a limit of seven days, if there is clinical improvement. Primary outcomes&#xD;
      will be duration of antibiotic therapy and antibiotic-free live days corrected for 1000 days&#xD;
      of hospitalization. Secondary outcomes will be costs, clinical cure rate, therapeutic&#xD;
      failure, 28-day mortality, 90-day mortality, in-hospital mortality, length of hospital stay,&#xD;
      nosocomial infection rate, recurrence of infection, and isolation of multidrug-resistant&#xD;
      bacteria&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">August 2018</completion_date>
  <primary_completion_date type="Actual">August 2018</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>Duration of antibiotic therapy for the first episode of infection</measure>
    <time_frame>1 year</time_frame>
    <description>Days of treatment with antibiotics after inclusion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total antibiotic exposure days per 1,000 days</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Costs of hospitalization</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Considering Brazilian market prices</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical cure rate</measure>
    <time_frame>28 days</time_frame>
    <description>Disappearance of clinical signs and symptoms present at inclusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Therapeutic failure</measure>
    <time_frame>28 days</time_frame>
    <description>Persistence or recurrence of the pathogen originally causing the infection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All cause 28-day mortality</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All cause 90-day mortality</measure>
    <time_frame>90 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of ICU stay</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nosocomial infection rate</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Isolation of multiresistant bacteria</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital mortality</measure>
    <time_frame>An average of 28 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">135</enrollment>
  <condition>Infection Systemic</condition>
  <arm_group>
    <arm_group_label>C-reactive Protein</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this group, the attending physicians will be instructed to follow the decision flowchart based on the CRP values. Antibiotic suspension will be encouraged when levels of this marker are &lt;35mg/L (if peak PCR below 100mg/L); or reduce 50% of the highest value (if PCR peak &gt; 100mg/L), with a limit of seven days, if there is clinical improvement. If a given patient has persistently elevated CRP levels (&gt; 100 mg/l or fall less than 50% relative to the time of inclusion), the investigators will encourage attending physicians to maintain antibiotics and to perform a careful search for persistent infection. In case of doubts, if the patient is well clinically and without signs of active infection, the duration of antibiotic therapy should be the same as suggested for the Best Practice group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Best Practice</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients will be initially treated according to the current protocols used in the intensive care units. Decisions about interruption or continuation of treatment will be made according to pre-established time and also according to the clinical evolution of the patients. CRP levels will not be measured and will not be considered in the decision to discontinue antimicrobials. Any decision ultimately rests with the clinical assistants. Suggestions on the suspension of antibiotics will be provided by the researchers as follows:&#xD;
7 full days for most infections&#xD;
10 full days for pneumonia caused by Gram negative non-fermenting bacteria or Gram negative bacteria carbapenemase producing.&#xD;
14 days of treatment for necrotizing pneumonia, confirmed by chest computed tomography.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>C-reactive protein</intervention_name>
    <description>PCR assays shall be performed daily on serum obtained from blood collected for routine intensive care examinations up to 2 days after antibiotic withdrawal. In the PCR group, antibiotic suspension will be encouraged when levels of this marker are &lt;35mg / L (if peak PCR below 100mg / L); or reduce 50% of the highest value (if PCR peak&gt; 100mg / L), with a limit of seven days, if there is clinical improvement.</description>
    <arm_group_label>C-reactive Protein</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Assumed or proven infection&#xD;
&#xD;
          -  Patient admitted to the unit participating in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with severe immunosuppression, such as severe neutropenia (&lt;500 neut/mm3),&#xD;
             transplantation of solid organs or cells hematopoietic, HIV infection with CD4+ &lt;&#xD;
             200/mm3&#xD;
&#xD;
          -  Patients with multiple trauma, burns or surgery grid size in the last 5 days (Except&#xD;
             surgery for focus control)&#xD;
&#xD;
          -  Use of antibiotics supposedly or proven to be effective against the infectious process&#xD;
             in for more than 48 hours.&#xD;
&#xD;
          -  Patients undergoing palliative care.&#xD;
&#xD;
          -  Patients with death expectancy for the next 24 hours.&#xD;
&#xD;
          -  Patients with bacteremia caused by Staphylococcus aureus or Candida spp&#xD;
&#xD;
          -  Patients with infections that are known to require prolonged antibiotic therapy&#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>Vandack Nobre, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Medical School of the Federal University of Minas Gerais</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Isabela Borges, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical School of the Federal University of Minas Gerais</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital das Clínicas - Universidade Federal de Minas Gerais</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>August 7, 2018</last_update_submitted>
  <last_update_submitted_qc>August 7, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Federal University of Minas Gerais</investigator_affiliation>
    <investigator_full_name>Vandack Alencar Nobre</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>Intensive care</keyword>
  <keyword>Sepsis</keyword>
  <keyword>Biomarkers</keyword>
  <keyword>C-reactive Protein</keyword>
  <keyword>Antimicrobial</keyword>
  <keyword>Systemic infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02987790
org study id: PCRxBestPractice
nct id: NCT02987790
lead sponsor: 
collaborator: 
has dmc: No
The judicious use of antibiotics is one of the main measures to limit the emergence of
      multidrug-resistant pathogen related to excessive antimicrobial use. A recent study
      demonstrated that C-reactive protein (CRP) was as useful as procalcitonin (PCT) in reducing
      the time of antibiotic therapy in adult septic patients treated in the ICU setting.
      Therefore, the present study proposes to compare the time of use of antimicrobials, costs of
      hospitalization and clinical outcomes of interest among a group of antibiotic therapy guided
      by serum levels of CRP and a group of therapy based on the best practices of antibiotic
      therapy (Best Practice).
All adult patients (aged> 17 years), hospitalized at the ICU (total of 50 beds) of the
      Hospital das Clínicas - UFMG, with an assumed or proven infection, will be considered for
      inclusion. Patients who meet the inclusion and exclusion criteria will be allocated randomly
      into one of the following groups: 1) PCR group: antibiotic therapy will be discontinued
      according to serum CRP levels; 2) "Best Practice" group, length of antibiotic therapy based
      on the most recent guidelines in the medical literature, according to the focus and / or
      causative micro-organism. PCR assays shall be performed daily on serum obtained from blood
      collected for routine intensive care examinations up to 2 days after antibiotic withdrawal.
      In the PCR group, antibiotic suspension will be encouraged when levels of this marker are
      <35mg / L (if peak PCR below 100mg / L); or reduce 50% of the highest value (if PCR peak >
      100mg / L), with a limit of seven days, if there is clinical improvement. Primary outcomes
      will be duration of antibiotic therapy and antibiotic-free live days corrected for 1000 days
      of hospitalization. Secondary outcomes will be costs, clinical cure rate, therapeutic
      failure, 28-day mortality, 90-day mortality, in-hospital mortality, length of hospital stay,
      nosocomial infection rate, recurrence of infection, and isolation of multidrug-resistant
      bacteria
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Duration of antibiotic therapy for the first episode of infection
time frame: 1 year
description: Days of treatment with antibiotics after inclusion
measure: Total antibiotic exposure days per 1,000 days
time frame: 1 year
measure: Costs of hospitalization
time frame: Through study completion, an average of 1 year
description: Considering Brazilian market prices
measure: Clinical cure rate
time frame: 28 days
description: Disappearance of clinical signs and symptoms present at inclusion
measure: Therapeutic failure
time frame: 28 days
description: Persistence or recurrence of the pathogen originally causing the infection.
measure: All cause 28-day mortality
time frame: 28 days
measure: All cause 90-day mortality
time frame: 90 days
measure: Length of ICU stay
time frame: 28 days
measure: Length of hospital stay
time frame: 28 days
measure: Nosocomial infection rate
time frame: 28 days
measure: Isolation of multiresistant bacteria
time frame: 28 days
measure: In-hospital mortality
time frame: An average of 28 days
arm group label: C-reactive Protein
arm group type: Experimental
description: In this group, the attending physicians will be instructed to follow the decision flowchart based on the CRP values. Antibiotic suspension will be encouraged when levels of this marker are <35mg/L (if peak PCR below 100mg/L); or reduce 50% of the highest value (if PCR peak > 100mg/L), with a limit of seven days, if there is clinical improvement. If a given patient has persistently elevated CRP levels (> 100 mg/l or fall less than 50% relative to the time of inclusion), the investigators will encourage attending physicians to maintain antibiotics and to perform a careful search for persistent infection. In case of doubts, if the patient is well clinically and without signs of active infection, the duration of antibiotic therapy should be the same as suggested for the Best Practice group.
arm group label: Best Practice
arm group type: No Intervention
description: Patients will be initially treated according to the current protocols used in the intensive care units. Decisions about interruption or continuation of treatment will be made according to pre-established time and also according to the clinical evolution of the patients. CRP levels will not be measured and will not be considered in the decision to discontinue antimicrobials. Any decision ultimately rests with the clinical assistants. Suggestions on the suspension of antibiotics will be provided by the researchers as follows:
7 full days for most infections
10 full days for pneumonia caused by Gram negative non-fermenting bacteria or Gram negative bacteria carbapenemase producing.
14 days of treatment for necrotizing pneumonia, confirmed by chest computed tomography.
intervention type: Other
intervention name: C-reactive protein
description: PCR assays shall be performed daily on serum obtained from blood collected for routine intensive care examinations up to 2 days after antibiotic withdrawal. In the PCR group, antibiotic suspension will be encouraged when levels of this marker are <35mg / L (if peak PCR below 100mg / L); or reduce 50% of the highest value (if PCR peak> 100mg / L), with a limit of seven days, if there is clinical improvement.
arm group label: C-reactive Protein
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Vandack Nobre, PhD
role: Study Director
affiliation: Medical School of the Federal University of Minas Gerais
last name: Isabela Borges, MSc
role: Principal Investigator
affiliation: Medical School of the Federal University of Minas Gerais
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Federal University of Minas Gerais
investigator full name: Vandack Alencar Nobre
investigator title: PhD
mesh term: Sepsis
sharing ipd: Undecided