<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/NCT01730066</url>
  </required_header>
  <id_info>
    <org_study_id>ProOncENT</org_study_id>
    <nct_id>NCT01730066</nct_id>
  </id_info>
  <brief_title>Probiotics Against Pathogenic Bacteria in Advanced ENT-Surgery</brief_title>
  <official_title>Probiotics for Reduction of Pathogenic Bacteria in Connection With Advanced Surgery in the Mouth, the Oropharynx, and on the Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Region Skane</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lund University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Region Skane</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Surgery in the mouth and oropharynx is performed in an area colonised by bacteria&#xD;
      non-pathogenic and pathogenic.&#xD;
&#xD;
      Antibiotics are used regularly resulting in disturbances in the intestinal microbiological&#xD;
      flora and consequently diarrhoea that can be troublesome. The use of antibiotics throughout&#xD;
      the hospital stay for these difficult cases represent a risk of development of resistant&#xD;
      strains.&#xD;
&#xD;
      Most of the patients have cancer diagnoses and have radiation therapy before surgery. This&#xD;
      increases the risk of the patients having pathogenic bacteria normally present in the lower&#xD;
      GI-tract.&#xD;
&#xD;
      The investigators have shown for ICU patients that treatment with probiotics reduces the&#xD;
      number of emerging enteral bacteria in the oropharynx and now the investigators will perform&#xD;
      an adjusted procedure for patients planned for large ear, nose, and throat (ENT) surgery.&#xD;
&#xD;
      Patients will preoperatively gurgle a suspension of probiotics and then swallow the&#xD;
      preparation.&#xD;
&#xD;
      Postoperatively the probiotics is given enterally and a eventually by mouth again.&#xD;
&#xD;
      Cultures will be taken from the oropharynx and tracheal secretions and the results will be&#xD;
      compared&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Longer surgical procedures require intubation and there is a potential risk of contaminating&#xD;
      the lower airways with pathogenic bacteria from the mouth and oropharynx.&#xD;
&#xD;
      Surgery including the mouth and the oropharynx is performed in an area that is colonised by&#xD;
      hundreds of different bacterial species. In the healthy person there is a balance between the&#xD;
      different microbes and possible pathogens are kept under control.&#xD;
&#xD;
      Patients that are subject to surgery in the mouth, oropharynx or neck area, most often have&#xD;
      cancer diagnoses. Preoperative treatment (mostly radiation) is done in most cases resulting&#xD;
      in a changed spectrum of bacteria in the mouth and oropharynx. Due to lowered appetite&#xD;
      increased difficulties to eat, in combination with cancer diagnosis, there is also a change&#xD;
      in cranial direction of the microbiological gut flora resulting in the presence of pathogens&#xD;
      such as Gram-negative bacteria. Those species may result in troublesome infections in the&#xD;
      postoperative period.&#xD;
&#xD;
      With healthy people pathogenic bacteria originating from the gastro/intestinal canal are&#xD;
      seldom found in the oropharynx, but those do occur among many patients.&#xD;
&#xD;
      Antibiotics are used prophylactic and for more extensive surgery, as micro vascular&#xD;
      procedures with free transplants of tissues, antibiotics are kept throughout the length of&#xD;
      stay (LOS) in hospital. This results in an increased risk for the development of resistant&#xD;
      bacteria and does result in changes in the GI flora in those patients. Diarrhoea occurs&#xD;
      frequently and are troublesome for the patients For ICU patients we have seen a reduction of&#xD;
      emerging enteric bacteria in patients given oral care with probiotics and this study will&#xD;
      explore the possibility of the same kind of positive effects in patients due for extensive&#xD;
      surgery performed during several hours.&#xD;
&#xD;
      Many of the patients will have a tracheostomy performed as part of the surgical procedure.&#xD;
&#xD;
      Patients will be randomised (1:1) to either no prophylaxis (standard procedure today) or to&#xD;
      preparation with a probiotic suspension fro the day before surgery until discharge from&#xD;
      hospital.&#xD;
&#xD;
      Preoperatively the patients will gurgle a suspension of probiotics and then swallow the&#xD;
      preparation.&#xD;
&#xD;
      Postoperatively the probiotics is given enterally and a eventually when the responsible&#xD;
      surgeon find it suitable by mouth again.&#xD;
&#xD;
      Cultures at inclusion, after intubation, and then on predefined days postoperatively to&#xD;
      compare bacterial flora in the oropharynx and in tracheal secretions.&#xD;
&#xD;
      Infectious parameters will be followed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">June 2020</completion_date>
  <primary_completion_date type="Actual">December 2019</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Differences in pathogenic bacteria in the oropharynx</measure>
    <time_frame>During hospitalization, anticipated mean time 12 days</time_frame>
    <description>Emerging and resident bacteria will be compared for the cultures taken in the oropharynx and from tracheal secretions in connection to a surgical intervention and postoperatively</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>White Blood Cell count</measure>
    <time_frame>During hospital stay, expected mean LOS 12 days</time_frame>
    <description>WBC taken pre-op and then on predefined days postoperatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C Reactive Protein</measure>
    <time_frame>Throughout the hospital stay, expected mean LOS 12 days</time_frame>
    <description>CRP taken pre-op and then on predefined days postoperatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Hospital stay</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected average of 2-3 weeks</time_frame>
    <description>Length of stay is recorded for the Hospital stay, and for those cases that have an extended post-operative period in the ICU, the length of the ICU stay will be recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>Six months</time_frame>
    <description>For participating patients the status of survival or non survival at days 28 and 180 (six months) will be recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diarrhoea and obstipation</measure>
    <time_frame>Throughout the hospital stay, expected mean LOS 12 days</time_frame>
    <description>As ICU patients tend to display diarrhoea as well as obstipation the frequency and consistency of stools will be recorded.&#xD;
Probiotics are anticipated to stabilise bowel function</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Advanced ENT Surgery</condition>
  <condition>Microbiological Flora in the Oropharynx and Lower Airways</condition>
  <arm_group>
    <arm_group_label>Probiotics</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will gurgle and swallow a mixture of probiotic bacteria preoperatively and given the same study product enterally postoperatively</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No intervention.What has been the standard procedure so far</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>L. plantarum 299 and L. plantarum 299v (+maltodextrin)</intervention_name>
    <description>Patients will be given a mixture of maltodextrin ( a starch product often used i alimentary products) and two strains of probiotic bacteria ( L. plantarum 299 and L. plantarum 299v ) dissolved in water. They will gurgle and swallow the suspension from the day before surgery. Postoperatively they will be given the probiotic mixture via a nasogastric tubing twice a day and when the responsible surgeon find it suitable also orally as described above. When they can swallow no study product is given through the nasogastric tube.&#xD;
Patients randomized 1:1 between groups</description>
    <arm_group_label>Probiotics</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Elective advanced and extensive ENT surgery&#xD;
&#xD;
          -  Adult patients (≥ 18 years)&#xD;
&#xD;
          -  Surgery requires general anesthesia and endotracheal intubation&#xD;
&#xD;
          -  Length of anesthesia ≥ 1,5 hours&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Ongoing treatment requiring infection in the lower respiratory tract&#xD;
&#xD;
          -  Chronic lung disease requiring oxygen treatment&#xD;
&#xD;
          -  Known immune deficiency&#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>Bengt Klarin, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lund University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lund University Hospital</name>
      <address>
        <city>Lund</city>
        <zip>SE 22185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <link>
    <url>http://www.probi.se</url>
    <description>Provider of study product</description>
  </link>
  <reference>
    <citation>Stjernquist-Desatnik A, Warfving H, Johansson ML. Persistence of Lactobacillus plantarum DSM 9843 on human tonsillar surface after oral administration in fermented oatmeal gruel. A pilot study. Acta Otolaryngol Suppl. 2000;543:215-9. doi: 10.1080/000164800454422.</citation>
    <PMID>10909023</PMID>
  </reference>
  <reference>
    <citation>Klarin B, Molin G, Jeppsson B, Larsson A. Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study. Crit Care. 2008;12(6):R136. doi: 10.1186/cc7109. Epub 2008 Nov 6.</citation>
    <PMID>18990201</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>October 8, 2020</last_update_submitted>
  <last_update_submitted_qc>October 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Probiotics</keyword>
  <keyword>Pathogenic enteric bacteria</keyword>
  <keyword>Oropharyngeal flora</keyword>
  <keyword>CRP</keyword>
  <keyword>WBC</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Results will be published in a scientific journal</ipd_description>
  </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/NCT01730066
org study id: ProOncENT
nct id: NCT01730066
lead sponsor: 
collaborator: 
has dmc: No
Surgery in the mouth and oropharynx is performed in an area colonised by bacteria
      non-pathogenic and pathogenic.

      Antibiotics are used regularly resulting in disturbances in the intestinal microbiological
      flora and consequently diarrhoea that can be troublesome. The use of antibiotics throughout
      the hospital stay for these difficult cases represent a risk of development of resistant
      strains.

      Most of the patients have cancer diagnoses and have radiation therapy before surgery. This
      increases the risk of the patients having pathogenic bacteria normally present in the lower
      GI-tract.

      The investigators have shown for ICU patients that treatment with probiotics reduces the
      number of emerging enteral bacteria in the oropharynx and now the investigators will perform
      an adjusted procedure for patients planned for large ear, nose, and throat (ENT) surgery.

      Patients will preoperatively gurgle a suspension of probiotics and then swallow the
      preparation.

      Postoperatively the probiotics is given enterally and a eventually by mouth again.

      Cultures will be taken from the oropharynx and tracheal secretions and the results will be
      compared
Longer surgical procedures require intubation and there is a potential risk of contaminating
      the lower airways with pathogenic bacteria from the mouth and oropharynx.

      Surgery including the mouth and the oropharynx is performed in an area that is colonised by
      hundreds of different bacterial species. In the healthy person there is a balance between the
      different microbes and possible pathogens are kept under control.

      Patients that are subject to surgery in the mouth, oropharynx or neck area, most often have
      cancer diagnoses. Preoperative treatment (mostly radiation) is done in most cases resulting
      in a changed spectrum of bacteria in the mouth and oropharynx. Due to lowered appetite
      increased difficulties to eat, in combination with cancer diagnosis, there is also a change
      in cranial direction of the microbiological gut flora resulting in the presence of pathogens
      such as Gram-negative bacteria. Those species may result in troublesome infections in the
      postoperative period.

      With healthy people pathogenic bacteria originating from the gastro/intestinal canal are
      seldom found in the oropharynx, but those do occur among many patients.

      Antibiotics are used prophylactic and for more extensive surgery, as micro vascular
      procedures with free transplants of tissues, antibiotics are kept throughout the length of
      stay (LOS) in hospital. This results in an increased risk for the development of resistant
      bacteria and does result in changes in the GI flora in those patients. Diarrhoea occurs
      frequently and are troublesome for the patients For ICU patients we have seen a reduction of
      emerging enteric bacteria in patients given oral care with probiotics and this study will
      explore the possibility of the same kind of positive effects in patients due for extensive
      surgery performed during several hours.

      Many of the patients will have a tracheostomy performed as part of the surgical procedure.

      Patients will be randomised (1:1) to either no prophylaxis (standard procedure today) or to
      preparation with a probiotic suspension fro the day before surgery until discharge from
      hospital.

      Preoperatively the patients will gurgle a suspension of probiotics and then swallow the
      preparation.

      Postoperatively the probiotics is given enterally and a eventually when the responsible
      surgeon find it suitable by mouth again.

      Cultures at inclusion, after intubation, and then on predefined days postoperatively to
      compare bacterial flora in the oropharynx and in tracheal secretions.

      Infectious parameters will be followed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Differences in pathogenic bacteria in the oropharynx
time frame: During hospitalization, anticipated mean time 12 days
description: Emerging and resident bacteria will be compared for the cultures taken in the oropharynx and from tracheal secretions in connection to a surgical intervention and postoperatively
measure: White Blood Cell count
time frame: During hospital stay, expected mean LOS 12 days
description: WBC taken pre-op and then on predefined days postoperatively
measure: C Reactive Protein
time frame: Throughout the hospital stay, expected mean LOS 12 days
description: CRP taken pre-op and then on predefined days postoperatively
measure: Length of Hospital stay
time frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3 weeks
description: Length of stay is recorded for the Hospital stay, and for those cases that have an extended post-operative period in the ICU, the length of the ICU stay will be recorded
measure: Survival
time frame: Six months
description: For participating patients the status of survival or non survival at days 28 and 180 (six months) will be recorded
measure: Diarrhoea and obstipation
time frame: Throughout the hospital stay, expected mean LOS 12 days
description: As ICU patients tend to display diarrhoea as well as obstipation the frequency and consistency of stools will be recorded.
Probiotics are anticipated to stabilise bowel function
arm group label: Probiotics
arm group type: Experimental
description: Patients will gurgle and swallow a mixture of probiotic bacteria preoperatively and given the same study product enterally postoperatively
arm group label: Control
arm group type: No Intervention
description: No intervention.What has been the standard procedure so far
intervention type: Dietary Supplement
intervention name: L. plantarum 299 and L. plantarum 299v (+maltodextrin)
description: Patients will be given a mixture of maltodextrin ( a starch product often used i alimentary products) and two strains of probiotic bacteria ( L. plantarum 299 and L. plantarum 299v ) dissolved in water. They will gurgle and swallow the suspension from the day before surgery. Postoperatively they will be given the probiotic mixture via a nasogastric tubing twice a day and when the responsible surgeon find it suitable also orally as described above. When they can swallow no study product is given through the nasogastric tube.
Patients randomized 1:1 between groups
arm group label: Probiotics
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bengt Klarin, MD, PhD
role: Principal Investigator
affiliation: Lund University Hospital
facility: 
country: Sweden
url: http://www.probi.se
description: Provider of study product
citation: Stjernquist-Desatnik A, Warfving H, Johansson ML. Persistence of Lactobacillus plantarum DSM 9843 on human tonsillar surface after oral administration in fermented oatmeal gruel. A pilot study. Acta Otolaryngol Suppl. 2000;543:215-9. doi: 10.1080/000164800454422.
PMID: 10909023
citation: Klarin B, Molin G, Jeppsson B, Larsson A. Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study. Crit Care. 2008;12(6):R136. doi: 10.1186/cc7109. Epub 2008 Nov 6.
PMID: 18990201
responsible party type: Sponsor
sharing ipd: Yes
ipd description: Results will be published in a scientific journal