<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/NCT03256708</url>
  </required_header>
  <id_info>
    <org_study_id>THE-2017-001</org_study_id>
    <nct_id>NCT03256708</nct_id>
  </id_info>
  <brief_title>Prevention of Antibiotic-Associated Diarrhoea With Prolardii</brief_title>
  <acronym>PAADI</acronym>
  <official_title>Double-blind Randomised Placebo-controlled Study of Prolardii Gastro-resistant (GR) Caps in the Prevention and Treatment of Antibiotic-associated Diarrhoea.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Therabel Pharma SA/NV</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ECSOR</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Therabel Pharma SA/NV</source>
  <oversight_info>
    <has_dmc>No</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>
      Prolardii contains intestinal bacteria, a yeast, a fructo-oligosaccharide and a plant extract&#xD;
      that can contribute to the intestinal comfort. This product could prevent the diarrhea which&#xD;
      sometimes occurs when the patient has to take antibiotics.&#xD;
&#xD;
      A total of 220 patients being prescribed antibiotics by general practitioners will be&#xD;
      included in the study and randomized into a Prolardii arm and a placebo arm.&#xD;
&#xD;
      The primary endpoint will be the overall frequency of diarrhea in the two treatment groups.&#xD;
      Acute diarrhea will be defined as the presence of three or more abnormally loose or watery&#xD;
      stools per day.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prolardii is a synbiotic (prebiotic and probiotic) formulation including 4 strains of living&#xD;
      lyophilized lactic bacteria (Lactobacillus rhamnosus GG, Bifidobacterium lactis B94,&#xD;
      Lactobacillus casei 5773 and Lactobacillus acidophilus LA3), a yeast (Saccharomyces&#xD;
      boulardii), a fructo-oligosaccharide (Actilight) and a dry extract of Inula helenium, a plant&#xD;
      that can contribute to the intestinal comfort.&#xD;
&#xD;
      Taking into account the international literature, we made the assumption that the combination&#xD;
      of probiotics and prebiotics into the same synbiotic product could improve the prevention of&#xD;
      antibiotic-associated diarrhea and could also attenuate the intestinal symptoms related to&#xD;
      the use of antibiotics. According to our knowledge this association has never been tested in&#xD;
      a double-blind, randomised, placebo-controlled study.&#xD;
&#xD;
      The study will be double-blind, parallel-group, randomized, multicentre and&#xD;
      placebo-controlled. A total of 220 patients being prescribed broad-spectrum antibiotics by&#xD;
      general practitioners will be included in the study and randomized (1:1) into a Prolardii arm&#xD;
      (2 capsules per day for 12 to 15 days) and a placebo arm (2 capsules per day for 12 to 15&#xD;
      days). There will be two medical visits (baseline visit and end-of-treatment visit) and one&#xD;
      follow-up phone call (4 weeks after the end of treatment). During the treatment, the patients&#xD;
      will filled in a diary card on a daily basis. They will record the number of bowel movements,&#xD;
      the quality of the stools, the solicited symptoms (flatulence, bloating, abdominal&#xD;
      pain/cramps, nausea and vomiting), their quality of life and the use of concomitant&#xD;
      medications.&#xD;
&#xD;
      The data will be collected in an electronic case report form. The sample size calculation was&#xD;
      based on the following assumptions: an attack rate in the placebo group situated in a range&#xD;
      between 20% and 25%, an efficacy of Prolardii of about 60%, a randomization ratio 1:1 between&#xD;
      the placebo and the active treatment group, a power of 80% and a Type I error value of 5%.&#xD;
      Taking into account these assumptions a total of at least 30 diarrhoea cases should be&#xD;
      reached all together in the two treatment groups, in order to ensure a sufficient power.&#xD;
&#xD;
      The primary endpoint will be the overall frequency of diarrhea in the two treatment groups.&#xD;
      Acute diarrhea will be defined as the presence of three or more abnormally loose or watery&#xD;
      stools per day.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">October 19, 2017</start_date>
  <completion_date type="Anticipated">September 2018</completion_date>
  <primary_completion_date type="Anticipated">September 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>
    <intervention_model_description>Double-blind parallel placebo-controlled randomized study</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Prevention of antibiotic-associated diarrhea</measure>
    <time_frame>Antibiotic treatment duration (7 to 10 days) + 5 days</time_frame>
    <description>Percentage of patients presenting an acute antibiotic-associated diarrhea</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of diarrhea</measure>
    <time_frame>Antibiotic treatment duration (7 to 10 days) + 5 days</time_frame>
    <description>Number of days of diarrhea</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of bowel movements</measure>
    <time_frame>Antibiotic treatment duration (7 to 10 days) + 5 days</time_frame>
    <description>Number of defecations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability of the study treatment</measure>
    <time_frame>Antibiotic treatment duration (7 to 10 days) + 5 days</time_frame>
    <description>Percentage of patients showing solicited symptoms (flatulence, bloating, abdominal pain/cramps, nausea and/or vomiting)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life of the patients</measure>
    <time_frame>Antibiotic treatment duration (7 to 10 days) + 5 days</time_frame>
    <description>Quality of life score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of the study treatment</measure>
    <time_frame>Antibiotic treatment duration (7 to 10 days) + 5 days</time_frame>
    <description>Percentage of patients with adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">220</enrollment>
  <condition>Antibiotic-associated Diarrhea</condition>
  <arm_group>
    <arm_group_label>Prolardii</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prolardii GR Caps includes 4 strains of living lyophilized lactic bacteria (Lactobacillus rhamnosus GG, Bifidobacterium lactis B94, Lactobacillus casei 5773 and Lactobacillus acidophilus LA3), a yeast (Saccharomyces boulardii), a fructo-oligosaccharide (Actilight) and a dry extract of Inula helenium.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Inactive ingredients</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Prolardii</intervention_name>
    <description>Prolardii: 2 capsules per day for 12 to 15 days</description>
    <arm_group_label>Prolardii</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inactive ingredients</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Male or female patient&#xD;
&#xD;
          -  Patient aged 18 to 65 years-old&#xD;
&#xD;
          -  Patient being prescribed broad spectrum antibiotics for a minimum period of 7 days and&#xD;
             a maximum period of 10 days. Broad spectrum antibiotics are aminopenicillins&#xD;
             (amoxicillin with or without clavulanic acid, ampicillin), cephalosporins (cefadroxil,&#xD;
             cephalexin, cefazolin, cefuroxime, cefotaxime, ceftazidime, ceftriaxone and&#xD;
             ceftaroline), fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin,&#xD;
             norfloxacin), tetracyclines (doxycycline, minocycline), nitrofurans (nitrofurantoin)&#xD;
             and/or antibacterial sulfonamides (co-trimoxazol).&#xD;
&#xD;
          -  Patient who the investigator believes that they can and will comply with the&#xD;
             requirements of the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient treated with antibiotics within 3 months before inclusion in the study&#xD;
&#xD;
          -  Pregnant or lactating woman&#xD;
&#xD;
          -  Woman wishing to be pregnant&#xD;
&#xD;
          -  Immunosuppressed subject&#xD;
&#xD;
          -  Subject having a central venous catheter&#xD;
&#xD;
          -  History of chronic diarrhoea&#xD;
&#xD;
          -  History of irritable bowel syndrome&#xD;
&#xD;
          -  History of Crohn's disease&#xD;
&#xD;
          -  History of ulcerative colitis&#xD;
&#xD;
          -  History of chronic constipation and/or chronic use of laxatives&#xD;
&#xD;
          -  Patient with a clinically-active malignancy.&#xD;
&#xD;
          -  Patient who participated in a clinical study in the previous three months&#xD;
&#xD;
          -  History of psychological disorder, mental dysfunction, alcohol or drug abuse or any&#xD;
             other factor which might interfere with the ability to cooperate in the study.&#xD;
&#xD;
          -  Patient who is not sufficiently motivated to engage on a follow-up period of&#xD;
             approximately 1.5 month, unable to complete the patient diary, or likely to travel or&#xD;
             to move before the end of the study&#xD;
&#xD;
          -  Intolerance to lactose&#xD;
&#xD;
          -  Difficulty or inability to swallow '00' size capsules&#xD;
&#xD;
          -  Allergy to one or several ingredients of Prolardii® GR Caps and in particular to&#xD;
             yeasts.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicolas Foucart</last_name>
    <role>Study Director</role>
    <affiliation>Marketing Manager</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ResearchLink</name>
      <address>
        <city>Linkebeek</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>April 1, 2018</last_update_submitted>
  <last_update_submitted_qc>April 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>antibiotic-associated diarrhea</keyword>
  <keyword>probiotic</keyword>
  <keyword>prebiotic</keyword>
  <keyword>placebo</keyword>
  <keyword>synbiotic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diarrhea</mesh_term>
  </condition_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/NCT03256708
org study id: THE-2017-001
nct id: NCT03256708
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Prolardii contains intestinal bacteria, a yeast, a fructo-oligosaccharide and a plant extract
      that can contribute to the intestinal comfort. This product could prevent the diarrhea which
      sometimes occurs when the patient has to take antibiotics.

      A total of 220 patients being prescribed antibiotics by general practitioners will be
      included in the study and randomized into a Prolardii arm and a placebo arm.

      The primary endpoint will be the overall frequency of diarrhea in the two treatment groups.
      Acute diarrhea will be defined as the presence of three or more abnormally loose or watery
      stools per day.
Prolardii is a synbiotic (prebiotic and probiotic) formulation including 4 strains of living
      lyophilized lactic bacteria (Lactobacillus rhamnosus GG, Bifidobacterium lactis B94,
      Lactobacillus casei 5773 and Lactobacillus acidophilus LA3), a yeast (Saccharomyces
      boulardii), a fructo-oligosaccharide (Actilight) and a dry extract of Inula helenium, a plant
      that can contribute to the intestinal comfort.

      Taking into account the international literature, we made the assumption that the combination
      of probiotics and prebiotics into the same synbiotic product could improve the prevention of
      antibiotic-associated diarrhea and could also attenuate the intestinal symptoms related to
      the use of antibiotics. According to our knowledge this association has never been tested in
      a double-blind, randomised, placebo-controlled study.

      The study will be double-blind, parallel-group, randomized, multicentre and
      placebo-controlled. A total of 220 patients being prescribed broad-spectrum antibiotics by
      general practitioners will be included in the study and randomized (1:1) into a Prolardii arm
      (2 capsules per day for 12 to 15 days) and a placebo arm (2 capsules per day for 12 to 15
      days). There will be two medical visits (baseline visit and end-of-treatment visit) and one
      follow-up phone call (4 weeks after the end of treatment). During the treatment, the patients
      will filled in a diary card on a daily basis. They will record the number of bowel movements,
      the quality of the stools, the solicited symptoms (flatulence, bloating, abdominal
      pain/cramps, nausea and vomiting), their quality of life and the use of concomitant
      medications.

      The data will be collected in an electronic case report form. The sample size calculation was
      based on the following assumptions: an attack rate in the placebo group situated in a range
      between 20% and 25%, an efficacy of Prolardii of about 60%, a randomization ratio 1:1 between
      the placebo and the active treatment group, a power of 80% and a Type I error value of 5%.
      Taking into account these assumptions a total of at least 30 diarrhoea cases should be
      reached all together in the two treatment groups, in order to ensure a sufficient power.

      The primary endpoint will be the overall frequency of diarrhea in the two treatment groups.
      Acute diarrhea will be defined as the presence of three or more abnormally loose or watery
      stools per day.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double-blind parallel placebo-controlled randomized study
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Prevention of antibiotic-associated diarrhea
time frame: Antibiotic treatment duration (7 to 10 days) + 5 days
description: Percentage of patients presenting an acute antibiotic-associated diarrhea
measure: Duration of diarrhea
time frame: Antibiotic treatment duration (7 to 10 days) + 5 days
description: Number of days of diarrhea
measure: Number of bowel movements
time frame: Antibiotic treatment duration (7 to 10 days) + 5 days
description: Number of defecations
measure: Tolerability of the study treatment
time frame: Antibiotic treatment duration (7 to 10 days) + 5 days
description: Percentage of patients showing solicited symptoms (flatulence, bloating, abdominal pain/cramps, nausea and/or vomiting)
measure: Quality of life of the patients
time frame: Antibiotic treatment duration (7 to 10 days) + 5 days
description: Quality of life score
measure: Safety of the study treatment
time frame: Antibiotic treatment duration (7 to 10 days) + 5 days
description: Percentage of patients with adverse events
arm group label: Prolardii
arm group type: Experimental
description: Prolardii GR Caps includes 4 strains of living lyophilized lactic bacteria (Lactobacillus rhamnosus GG, Bifidobacterium lactis B94, Lactobacillus casei 5773 and Lactobacillus acidophilus LA3), a yeast (Saccharomyces boulardii), a fructo-oligosaccharide (Actilight) and a dry extract of Inula helenium.
arm group label: Placebo
arm group type: Placebo Comparator
description: Inactive ingredients
intervention type: Dietary Supplement
intervention name: Prolardii
description: Prolardii: 2 capsules per day for 12 to 15 days
arm group label: Prolardii
intervention type: Dietary Supplement
intervention name: Placebo
description: Inactive ingredients
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Nicolas Foucart
role: Study Director
affiliation: Marketing Manager
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Diarrhea
sharing ipd: No