<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/NCT03794765</url>
  </required_header>
  <id_info>
    <org_study_id>NK/5147/DM</org_study_id>
    <nct_id>NCT03794765</nct_id>
  </id_info>
  <brief_title>Antibiotics as an Adjuvant in Patients With Acute Severe Ulcerative Colitis</brief_title>
  <acronym>AAASUC</acronym>
  <official_title>Use of Antibiotics as an Adjuvant in Patients With Acute Severe Ulcerative Colitis: A Randomised Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Postgraduate Institute of Medical Education and Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Postgraduate Institute of Medical Education and Research</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>
      The study is planned as a randomised control trial to study the adjuvant use of antibiotics&#xD;
      (ceftriaxone and metronidazole) to achieve a clinical response in hospitalised patients with&#xD;
      acute severe ulcerative colitis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All patients with active ulcerative colitis who present to the Outpatient department or the&#xD;
      emergency services of PGIMER shall be screened. Those patients who have acute severe&#xD;
      ulcerative colitis shall be assessed for inclusion into the study. Patients who fulfil the&#xD;
      eligibility criteria will be randomised into two groups.&#xD;
&#xD;
      Group A will include patients in the intervention arm. They will be given intravenous&#xD;
      antibiotics for three days. Injection ceftriaxone 1 gm will be prepared by reconstitution of&#xD;
      the crystallized powder form in 100 ml of normal saline. This preparation will then be&#xD;
      infused slowly over thirty minutes, after intradermal testing for hypersensitivity. Inj&#xD;
      ceftriaxone 1gm IV will be given twelve hourly. Injection metronidazole 500 mg is available&#xD;
      from pharmacies in solutions of 100 ml. It will be infused slowly over thirty minutes, three&#xD;
      times per day, after intradermal testing for hypersensitivity. Both the drugs will be given&#xD;
      for five days. In addition, they will receive the standard of care mentioned below.&#xD;
&#xD;
      Group B will include patients from the placebo arm. They will be given the standard of care&#xD;
      as mentioned below. In addition, they will be infused 0.9 % saline of similar quantity,&#xD;
      colour, and from similarly shaped bottles, for three days after sensitivity testing with the&#xD;
      saline.&#xD;
&#xD;
      Detailed history and examination shall be done for all the patients. History regarding the&#xD;
      stool output, any systemic symptoms, prior treatment history and history regarding any&#xD;
      precipitant for the acute episode shall be taken. Examination will include vitals (pulse&#xD;
      rate, blood pressure, temperature), general physical examination as well as an abdominal&#xD;
      examination. All patients will undergo blood investigations on all three days. This includes&#xD;
      a complete blood counts, kidney function tests, serum electrolytes, albumin, C-reactive&#xD;
      protein, osteopontin, blood culture. Stool routine microscopic examination, fecal&#xD;
      calprotectin, stool assay for clostridium difficile toxin will be done. X ray abdomen will be&#xD;
      done on all three days to monitor the diameter of transverse colon. Patients will undergo an&#xD;
      unprepared sigmoidoscopy with minimal air insufflation and mucosal biopsy. Biopsies will be&#xD;
      taken for histological examination. Procalcitonin, fecal calprotectin and CRP shall be&#xD;
      repeated on day 3 of admission.&#xD;
&#xD;
      All patients will be prescribed the standard treatment for acute severe colitis, which&#xD;
      includes intravenous steroids (Inj Hydrocortisone 100 mg IV QID or Inj Methyprednisolone 60&#xD;
      mg iv OD), anticoagulation, (Inj Unfractionated heparin 5000 IU S/C BD), intravenous fluid&#xD;
      supplementation and correction of electrolytes. Patients will be allowed orally and will be&#xD;
      prescribed a diet of 25-30 kcal /kg/day.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Actual">April 4, 2020</completion_date>
  <primary_completion_date type="Actual">March 4, 2020</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical response as defined by the Oxford's criteria</measure>
    <time_frame>48 hours</time_frame>
    <description>Patients will be defined as complete responders, partial responders or non-responders</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion needing second line therapy</measure>
    <time_frame>28 days</time_frame>
    <description>Second line therapy : Intravenous Infliximab, Intravenous cyclosporine or others</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion needing colectomy</measure>
    <time_frame>28 days</time_frame>
    <description>Number of patients in each group needing colectomy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>28 days</time_frame>
    <description>Number of patients in having mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospital stay</measure>
    <time_frame>28 days</time_frame>
    <description>Length of hospital stay in each group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum CRP levels</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Mayo disease severity index</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients with Reduction in fecal calprotectin by &gt;100 mcg/mg</measure>
    <time_frame>48 hours</time_frame>
    <description>Number of patients in each group having the predefined decline in fecal calprotectin</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Ulcerative Colitis</condition>
  <condition>Inflammatory Bowel Diseases</condition>
  <condition>Acute Severe Colitis</condition>
  <arm_group>
    <arm_group_label>Antibiotic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Standard of Care (steroids, prophylactic anticoagulation, oral nutrition) And Antibiotics (Inj Ceftriaxone 1 gram intravenous twice daily And Inj Metronidazole 500 mg intravenous thrice daily) for initial 48 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Standard of care (steroids, prophylactic anticoagulation, oral nutrition) And Placebo infusions similar to the active drugs</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ceftriaxone</intervention_name>
    <description>Injection ceftriaxone 1 gm will be prepared by reconstitution of the crystallised powder form in 100 ml of normal saline. This preparation will then be infused slowly over thirty minutes, after intradermal testing for hypersensitivity. Inj ceftriaxone 1gm IV will be given twelve hourly.</description>
    <arm_group_label>Antibiotic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metronidazole</intervention_name>
    <description>Injection metronidazole 500 mg is available from pharmacies in solutions of 100 ml. It will be infused slowly over thirty minutes, three times per day</description>
    <arm_group_label>Antibiotic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo infusion</intervention_name>
    <description>Similar placebo infusion</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Acute severe ulcerative colitis as described in European Crohn's and Colitis&#xD;
             Organisation (ECCO) guidelines (adapted from Truelove and Witts)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who deny consent&#xD;
&#xD;
          -  Age&lt;=12 years&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Severe uncontrolled comorbidities like diabetes mellitus, hypertension, coronary&#xD;
             artery disease, chronic liver disease, chronic kidney disease, etc&#xD;
&#xD;
          -  History of antibiotic use in the past one month, excluding those who may have received&#xD;
             a single dose of antibiotic in past 24 hrs&#xD;
&#xD;
          -  History of hypersensitivity or contraindication to steroids or the test drugs&#xD;
&#xD;
          -  Presence of toxic megacolon as defined by transverse colon diameter more than 5.5cm on&#xD;
             abdominal X-ray&#xD;
&#xD;
          -  Patients with evidence of sepsis or active infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vishal Sharma</last_name>
    <role>Principal Investigator</role>
    <affiliation>Postgraduate Institute of Medical Education and Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shubhra Mishra</last_name>
    <role>Principal Investigator</role>
    <affiliation>Postgraduate Institute of Medical Education and Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Postgraduate Institute of Medical Education and Research</name>
      <address>
        <city>Chandigarh</city>
        <zip>160012</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <results_reference>
    <citation>Mishra S, Mandavdhare HS, Singh H, Choudhury A, Shah J, Ram S, Kalsi D, Samanta J, Prasad KK, Sharma AK, Dutta U, Sharma V. Adjuvant use of combination of antibiotics in acute severe ulcerative colitis: A placebo controlled randomized trial. Expert Rev Anti Infect Ther. 2021 Jul;19(7):949-955. doi: 10.1080/14787210.2021.1856656. Epub 2020 Dec 14.</citation>
    <PMID>33245002</PMID>
  </results_reference>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>December 9, 2020</last_update_submitted>
  <last_update_submitted_qc>December 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
    <investigator_full_name>Vishal Sharma</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Antibiotics</keyword>
  <keyword>Ceftriaxone</keyword>
  <keyword>Metronidazole</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metronidazole</mesh_term>
    <mesh_term>Ceftriaxone</mesh_term>
  </intervention_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/NCT03794765
org study id: NK/5147/DM
nct id: NCT03794765
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study is planned as a randomised control trial to study the adjuvant use of antibiotics
      (ceftriaxone and metronidazole) to achieve a clinical response in hospitalised patients with
      acute severe ulcerative colitis
All patients with active ulcerative colitis who present to the Outpatient department or the
      emergency services of PGIMER shall be screened. Those patients who have acute severe
      ulcerative colitis shall be assessed for inclusion into the study. Patients who fulfil the
      eligibility criteria will be randomised into two groups.

      Group A will include patients in the intervention arm. They will be given intravenous
      antibiotics for three days. Injection ceftriaxone 1 gm will be prepared by reconstitution of
      the crystallized powder form in 100 ml of normal saline. This preparation will then be
      infused slowly over thirty minutes, after intradermal testing for hypersensitivity. Inj
      ceftriaxone 1gm IV will be given twelve hourly. Injection metronidazole 500 mg is available
      from pharmacies in solutions of 100 ml. It will be infused slowly over thirty minutes, three
      times per day, after intradermal testing for hypersensitivity. Both the drugs will be given
      for five days. In addition, they will receive the standard of care mentioned below.

      Group B will include patients from the placebo arm. They will be given the standard of care
      as mentioned below. In addition, they will be infused 0.9 % saline of similar quantity,
      colour, and from similarly shaped bottles, for three days after sensitivity testing with the
      saline.

      Detailed history and examination shall be done for all the patients. History regarding the
      stool output, any systemic symptoms, prior treatment history and history regarding any
      precipitant for the acute episode shall be taken. Examination will include vitals (pulse
      rate, blood pressure, temperature), general physical examination as well as an abdominal
      examination. All patients will undergo blood investigations on all three days. This includes
      a complete blood counts, kidney function tests, serum electrolytes, albumin, C-reactive
      protein, osteopontin, blood culture. Stool routine microscopic examination, fecal
      calprotectin, stool assay for clostridium difficile toxin will be done. X ray abdomen will be
      done on all three days to monitor the diameter of transverse colon. Patients will undergo an
      unprepared sigmoidoscopy with minimal air insufflation and mucosal biopsy. Biopsies will be
      taken for histological examination. Procalcitonin, fecal calprotectin and CRP shall be
      repeated on day 3 of admission.

      All patients will be prescribed the standard treatment for acute severe colitis, which
      includes intravenous steroids (Inj Hydrocortisone 100 mg IV QID or Inj Methyprednisolone 60
      mg iv OD), anticoagulation, (Inj Unfractionated heparin 5000 IU S/C BD), intravenous fluid
      supplementation and correction of electrolytes. Patients will be allowed orally and will be
      prescribed a diet of 25-30 kcal /kg/day.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Clinical response as defined by the Oxford's criteria
time frame: 48 hours
description: Patients will be defined as complete responders, partial responders or non-responders
measure: Proportion needing second line therapy
time frame: 28 days
description: Second line therapy : Intravenous Infliximab, Intravenous cyclosporine or others
measure: Proportion needing colectomy
time frame: 28 days
description: Number of patients in each group needing colectomy
measure: Mortality
time frame: 28 days
description: Number of patients in having mortality
measure: Duration of hospital stay
time frame: 28 days
description: Length of hospital stay in each group
measure: Change in serum CRP levels
time frame: 48 hours
measure: Change in Mayo disease severity index
time frame: 48 hours
measure: Patients with Reduction in fecal calprotectin by >100 mcg/mg
time frame: 48 hours
description: Number of patients in each group having the predefined decline in fecal calprotectin
arm group label: Antibiotic
arm group type: Experimental
description: Standard of Care (steroids, prophylactic anticoagulation, oral nutrition) And Antibiotics (Inj Ceftriaxone 1 gram intravenous twice daily And Inj Metronidazole 500 mg intravenous thrice daily) for initial 48 hours
arm group label: Placebo
arm group type: Placebo Comparator
description: Standard of care (steroids, prophylactic anticoagulation, oral nutrition) And Placebo infusions similar to the active drugs
intervention type: Drug
intervention name: Ceftriaxone
description: Injection ceftriaxone 1 gm will be prepared by reconstitution of the crystallised powder form in 100 ml of normal saline. This preparation will then be infused slowly over thirty minutes, after intradermal testing for hypersensitivity. Inj ceftriaxone 1gm IV will be given twelve hourly.
arm group label: Antibiotic
intervention type: Drug
intervention name: Metronidazole
description: Injection metronidazole 500 mg is available from pharmacies in solutions of 100 ml. It will be infused slowly over thirty minutes, three times per day
arm group label: Antibiotic
intervention type: Other
intervention name: Placebo infusion
description: Similar placebo infusion
arm group label: Placebo
criteria: 
gender: All
minimum age: 13 Years
maximum age: N/A
healthy volunteers: No
last name: Vishal Sharma
role: Principal Investigator
affiliation: Postgraduate Institute of Medical Education and Research
last name: Shubhra Mishra
role: Principal Investigator
affiliation: Postgraduate Institute of Medical Education and Research
facility: 
country: India
citation: Mishra S, Mandavdhare HS, Singh H, Choudhury A, Shah J, Ram S, Kalsi D, Samanta J, Prasad KK, Sharma AK, Dutta U, Sharma V. Adjuvant use of combination of antibiotics in acute severe ulcerative colitis: A placebo controlled randomized trial. Expert Rev Anti Infect Ther. 2021 Jul;19(7):949-955. doi: 10.1080/14787210.2021.1856656. Epub 2020 Dec 14.
PMID: 33245002
responsible party type: Principal Investigator
investigator affiliation: Postgraduate Institute of Medical Education and Research
investigator full name: Vishal Sharma
investigator title: Assistant Professor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Inflammatory Bowel Diseases
mesh term: Ulcer
mesh term: Metronidazole
mesh term: Ceftriaxone
sharing ipd: Undecided