<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/NCT04491799</url>
  </required_header>
  <id_info>
    <org_study_id>Si056/2019</org_study_id>
    <nct_id>NCT04491799</nct_id>
  </id_info>
  <brief_title>Fecal Calprotectin Level in Patients With Nosocomial Diarrhea</brief_title>
  <official_title>Fecal Calprotectin Level in Differentiating Between Inflammatory and Non-inflammatory Diarrhea in Patients With Nosocomial Diarrhea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mahidol University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mahidol University</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>
      Nosocomial diarrhea is a common problem.There are multiple ethiologies of nosocomial diarrhea&#xD;
      in which can be divided into inflammatory and non inflammatory diarrhea. Fecal calprotectin&#xD;
      is a good marker to identify inflammatory diarrhea in outpatient setting; for example,&#xD;
      differentiating inflammatory bowel disease and irritable bowel syndrome. Its performance in&#xD;
      inpatient setting has not been well established. This study aim to determine the efficacy of&#xD;
      fecal calprotectin in distinguishing inflammatory nosocomial diarrhea from non-inflammatory&#xD;
      nosocomial diarrhea.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, cross-sectional, and observational study. The patients with nosocomial&#xD;
      diarrhea whose stool samples are sent for stool examination and Clostridium difficile toxin&#xD;
      by their treating physicians will be recruited. Their leftover stool samples will be kept at&#xD;
      - 80 c and will be measured for calprotectin level at the end of study. The patients will be&#xD;
      treated by their treating physicians. They will be classified into 2 groups - inflammatory&#xD;
      and non-inflammatory diarrhea.&#xD;
&#xD;
      The inflammatory diarrhea will be defined if 1) positive for C. difficile toxin or 2) stool&#xD;
      WBC more than 5/HPF or 3) inflammatory mucosa or ulceration noted on colonoscopy.&#xD;
&#xD;
      The noninflammatory diarrhea will be defined if 1)negative for C. difficile toxin and 2) no&#xD;
      WBC on stool examination and 3) dramatic response to diet adjustment or 4) no mucosal&#xD;
      inflammation or ulceration if colonoscopy is performed&#xD;
&#xD;
      The patients who do not respond to diet modification, but do not undergo colonoscopy will be&#xD;
      excluded because the definite diagnosis cannot be made.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Actual">October 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Fecal calprotectin levels</measure>
    <time_frame>1 day</time_frame>
    <description>Compare fecal calprotectin levels in patients with inflammatory nosocomial diarrhea and non-inflammatory nosocomial diarrhea</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prognosis of hospitalized patients with nosocomial diarrhea.</measure>
    <time_frame>30 days</time_frame>
    <description>Correlation of fecal calprotectin levels and prognosis of hospitalized patients with nosocomial diarrhea.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">135</enrollment>
  <condition>Diarrhea</condition>
  <condition>Calprotectin</condition>
  <arm_group>
    <arm_group_label>Nosocomial diarrhea</arm_group_label>
    <description>Patients who are hospitalized and develop diarrhea after 72 hours of hospitalization.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Fecal calprotectin</intervention_name>
    <description>Fecal calprotectin is a protein found in human neutrophils, and it is released during active periods of inflammation of intestine. The sensitivity and specificity has been reported at 93% and 96%, respectively in differentiating inflammatory bowel disease from irritable bowel syndrome in outpatient setting.</description>
    <arm_group_label>Nosocomial diarrhea</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Stool examination Stool C.difficile toxin Fecal calprotectin&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Inpatients in Siriraj hospital, Bangkok, Thailand&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age more than 18 hear&#xD;
&#xD;
          -  Diarrhea more than 3 time per day after admitted in hospital more than 72 hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  intraabdominal pressure more than 12 mmHg&#xD;
&#xD;
          -  patient on chemotherapy with neutropenia ,ANC less than 1,000/mm3&#xD;
&#xD;
          -  patients whose definite diagnosis cannot be obtained&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Julajak Limsrivilai, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Siriraj Hospital, Mahidol University, Bangkok, Thailand.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Siriraj hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10700</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <reference>
    <citation>Pawlowski SW, Warren CA, Guerrant R. Diagnosis and treatment of acute or persistent diarrhea. Gastroenterology. 2009 May;136(6):1874-86. doi: 10.1053/j.gastro.2009.02.072. Epub 2009 May 7.</citation>
    <PMID>19457416</PMID>
  </reference>
  <reference>
    <citation>Reintam Blaser A, Deane AM, Fruhwald S. Diarrhoea in the critically ill. Curr Opin Crit Care. 2015 Apr;21(2):142-53. doi: 10.1097/MCC.0000000000000188.</citation>
    <PMID>25692805</PMID>
  </reference>
  <reference>
    <citation>Chang SJ, Huang HH. Diarrhea in enterally fed patients: blame the diet? Curr Opin Clin Nutr Metab Care. 2013 Sep;16(5):588-94. doi: 10.1097/MCO.0b013e328363bcaf.</citation>
    <PMID>23799327</PMID>
  </reference>
  <reference>
    <citation>Bartlett JG. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med. 2002 Jan 31;346(5):334-9. doi: 10.1056/NEJMcp011603. No abstract available.</citation>
    <PMID>11821511</PMID>
  </reference>
  <reference>
    <citation>Siciliano RF, Castelli JB, Randi BA, Vieira RD, Strabelli TM. Cytomegalovirus colitis in immunocompetent critically ill patients. Int J Infect Dis. 2014 Mar;20:71-3. doi: 10.1016/j.ijid.2013.11.008. Epub 2014 Jan 6.</citation>
    <PMID>24406737</PMID>
  </reference>
  <reference>
    <citation>Manabe YC, Vinetz JM, Moore RD, Merz C, Charache P, Bartlett JG. Clostridium difficile colitis: an efficient clinical approach to diagnosis. Ann Intern Med. 1995 Dec 1;123(11):835-40. doi: 10.7326/0003-4819-123-11-199512010-00004.</citation>
    <PMID>7486465</PMID>
  </reference>
  <reference>
    <citation>Crobach MJ, Dekkers OM, Wilcox MH, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin Microbiol Infect. 2009 Dec;15(12):1053-66. doi: 10.1111/j.1469-0691.2009.03098.x.</citation>
    <PMID>19929972</PMID>
  </reference>
  <reference>
    <citation>van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010 Jul 15;341:c3369. doi: 10.1136/bmj.c3369.</citation>
    <PMID>20634346</PMID>
  </reference>
  <reference>
    <citation>Menees SB, Powell C, Kurlander J, Goel A, Chey WD. A meta-analysis of the utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS. Am J Gastroenterol. 2015 Mar;110(3):444-54. doi: 10.1038/ajg.2015.6. Epub 2015 Mar 3.</citation>
    <PMID>25732419</PMID>
  </reference>
  <reference>
    <citation>Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N, Sandborn WJ, Feagan BG. C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2015 Jun;110(6):802-19; quiz 820. doi: 10.1038/ajg.2015.120. Epub 2015 May 12.</citation>
    <PMID>25964225</PMID>
  </reference>
  <reference>
    <citation>Whitehead SJ, Shipman KE, Cooper M, Ford C, Gama R. Is there any value in measuring faecal calprotectin in Clostridium difficile positive faecal samples? J Med Microbiol. 2014 Apr;63(Pt 4):590-593. doi: 10.1099/jmm.0.067389-0. Epub 2014 Jan 25.</citation>
    <PMID>24464697</PMID>
  </reference>
  <reference>
    <citation>Popiel KY, Gheorghe R, Eastmond J, Miller MA. Usefulness of Adjunctive Fecal Calprotectin and Serum Procalcitonin in Individuals Positive for Clostridium difficile Toxin Gene by PCR Assay. J Clin Microbiol. 2015 Nov;53(11):3667-9. doi: 10.1128/JCM.02230-15. Epub 2015 Sep 9.</citation>
    <PMID>26354814</PMID>
  </reference>
  <reference>
    <citation>Barbut F, Gouot C, Lapidus N, Suzon L, Syed-Zaidi R, Lalande V, Eckert C. Faecal lactoferrin and calprotectin in patients with Clostridium difficile infection: a case-control study. Eur J Clin Microbiol Infect Dis. 2017 Dec;36(12):2423-2430. doi: 10.1007/s10096-017-3080-y. Epub 2017 Aug 12.</citation>
    <PMID>28801865</PMID>
  </reference>
  <reference>
    <citation>Swale A, Miyajima F, Roberts P, Hall A, Little M, Beadsworth MB, Beeching NJ, Kolamunnage-Dona R, Parry CM, Pirmohamed M. Calprotectin and lactoferrin faecal levels in patients with Clostridium difficile infection (CDI): a prospective cohort study. PLoS One. 2014 Aug 29;9(8):e106118. doi: 10.1371/journal.pone.0106118. eCollection 2014.</citation>
    <PMID>25170963</PMID>
  </reference>
  <reference>
    <citation>Kim J, Kim H, Oh HJ, Kim HS, Hwang YJ, Yong D, Jeong SH, Lee K. Fecal Calprotectin Level Reflects the Severity of Clostridium difficile Infection. Ann Lab Med. 2017 Jan;37(1):53-57. doi: 10.3343/alm.2017.37.1.53.</citation>
    <PMID>27834066</PMID>
  </reference>
  <reference>
    <citation>Peretz A, Tkhawkho L, Pastukh N, Brodsky D, Halevi CN, Nitzan O. Correlation between fecal calprotectin levels, disease severity and the hypervirulent ribotype 027 strain in patients with Clostridium difficile infection. BMC Infect Dis. 2016 Jun 22;16:309. doi: 10.1186/s12879-016-1618-8.</citation>
    <PMID>27334992</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>April 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <last_update_submitted>April 6, 2021</last_update_submitted>
  <last_update_submitted_qc>April 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mahidol University</investigator_affiliation>
    <investigator_full_name>Julajak Limsrivilai</investigator_full_name>
    <investigator_title>Assist.Professor</investigator_title>
  </responsible_party>
  <keyword>Nosocomial diarrhea</keyword>
  <keyword>Fecal calprotectin</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 24, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT04491799/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04491799
org study id: Si056/2019
nct id: NCT04491799
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Nosocomial diarrhea is a common problem.There are multiple ethiologies of nosocomial diarrhea
      in which can be divided into inflammatory and non inflammatory diarrhea. Fecal calprotectin
      is a good marker to identify inflammatory diarrhea in outpatient setting; for example,
      differentiating inflammatory bowel disease and irritable bowel syndrome. Its performance in
      inpatient setting has not been well established. This study aim to determine the efficacy of
      fecal calprotectin in distinguishing inflammatory nosocomial diarrhea from non-inflammatory
      nosocomial diarrhea.
This is a prospective, cross-sectional, and observational study. The patients with nosocomial
      diarrhea whose stool samples are sent for stool examination and Clostridium difficile toxin
      by their treating physicians will be recruited. Their leftover stool samples will be kept at
      - 80 c and will be measured for calprotectin level at the end of study. The patients will be
      treated by their treating physicians. They will be classified into 2 groups - inflammatory
      and non-inflammatory diarrhea.

      The inflammatory diarrhea will be defined if 1) positive for C. difficile toxin or 2) stool
      WBC more than 5/HPF or 3) inflammatory mucosa or ulceration noted on colonoscopy.

      The noninflammatory diarrhea will be defined if 1)negative for C. difficile toxin and 2) no
      WBC on stool examination and 3) dramatic response to diet adjustment or 4) no mucosal
      inflammation or ulceration if colonoscopy is performed

      The patients who do not respond to diet modification, but do not undergo colonoscopy will be
      excluded because the definite diagnosis cannot be made.
observational model: Cohort
time perspective: Prospective
measure: Fecal calprotectin levels
time frame: 1 day
description: Compare fecal calprotectin levels in patients with inflammatory nosocomial diarrhea and non-inflammatory nosocomial diarrhea
measure: Prognosis of hospitalized patients with nosocomial diarrhea.
time frame: 30 days
description: Correlation of fecal calprotectin levels and prognosis of hospitalized patients with nosocomial diarrhea.
arm group label: Nosocomial diarrhea
description: Patients who are hospitalized and develop diarrhea after 72 hours of hospitalization.
intervention type: Diagnostic Test
intervention name: Fecal calprotectin
description: Fecal calprotectin is a protein found in human neutrophils, and it is released during active periods of inflammation of intestine. The sensitivity and specificity has been reported at 93% and 96%, respectively in differentiating inflammatory bowel disease from irritable bowel syndrome in outpatient setting.
arm group label: Nosocomial diarrhea
Stool examination Stool C.difficile toxin Fecal calprotectin
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Julajak Limsrivilai, MD, MSc
role: Principal Investigator
affiliation: Siriraj Hospital, Mahidol University, Bangkok, Thailand.
facility: 
country: Thailand
citation: Pawlowski SW, Warren CA, Guerrant R. Diagnosis and treatment of acute or persistent diarrhea. Gastroenterology. 2009 May;136(6):1874-86. doi: 10.1053/j.gastro.2009.02.072. Epub 2009 May 7.
PMID: 19457416
citation: Reintam Blaser A, Deane AM, Fruhwald S. Diarrhoea in the critically ill. Curr Opin Crit Care. 2015 Apr;21(2):142-53. doi: 10.1097/MCC.0000000000000188.
PMID: 25692805
citation: Chang SJ, Huang HH. Diarrhea in enterally fed patients: blame the diet? Curr Opin Clin Nutr Metab Care. 2013 Sep;16(5):588-94. doi: 10.1097/MCO.0b013e328363bcaf.
PMID: 23799327
citation: Bartlett JG. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med. 2002 Jan 31;346(5):334-9. doi: 10.1056/NEJMcp011603. No abstract available.
PMID: 11821511
citation: Siciliano RF, Castelli JB, Randi BA, Vieira RD, Strabelli TM. Cytomegalovirus colitis in immunocompetent critically ill patients. Int J Infect Dis. 2014 Mar;20:71-3. doi: 10.1016/j.ijid.2013.11.008. Epub 2014 Jan 6.
PMID: 24406737
citation: Manabe YC, Vinetz JM, Moore RD, Merz C, Charache P, Bartlett JG. Clostridium difficile colitis: an efficient clinical approach to diagnosis. Ann Intern Med. 1995 Dec 1;123(11):835-40. doi: 10.7326/0003-4819-123-11-199512010-00004.
PMID: 7486465
citation: Crobach MJ, Dekkers OM, Wilcox MH, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin Microbiol Infect. 2009 Dec;15(12):1053-66. doi: 10.1111/j.1469-0691.2009.03098.x.
PMID: 19929972
citation: van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010 Jul 15;341:c3369. doi: 10.1136/bmj.c3369.
PMID: 20634346
citation: Menees SB, Powell C, Kurlander J, Goel A, Chey WD. A meta-analysis of the utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS. Am J Gastroenterol. 2015 Mar;110(3):444-54. doi: 10.1038/ajg.2015.6. Epub 2015 Mar 3.
PMID: 25732419
citation: Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N, Sandborn WJ, Feagan BG. C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2015 Jun;110(6):802-19; quiz 820. doi: 10.1038/ajg.2015.120. Epub 2015 May 12.
PMID: 25964225
citation: Whitehead SJ, Shipman KE, Cooper M, Ford C, Gama R. Is there any value in measuring faecal calprotectin in Clostridium difficile positive faecal samples? J Med Microbiol. 2014 Apr;63(Pt 4):590-593. doi: 10.1099/jmm.0.067389-0. Epub 2014 Jan 25.
PMID: 24464697
citation: Popiel KY, Gheorghe R, Eastmond J, Miller MA. Usefulness of Adjunctive Fecal Calprotectin and Serum Procalcitonin in Individuals Positive for Clostridium difficile Toxin Gene by PCR Assay. J Clin Microbiol. 2015 Nov;53(11):3667-9. doi: 10.1128/JCM.02230-15. Epub 2015 Sep 9.
PMID: 26354814
citation: Barbut F, Gouot C, Lapidus N, Suzon L, Syed-Zaidi R, Lalande V, Eckert C. Faecal lactoferrin and calprotectin in patients with Clostridium difficile infection: a case-control study. Eur J Clin Microbiol Infect Dis. 2017 Dec;36(12):2423-2430. doi: 10.1007/s10096-017-3080-y. Epub 2017 Aug 12.
PMID: 28801865
citation: Swale A, Miyajima F, Roberts P, Hall A, Little M, Beadsworth MB, Beeching NJ, Kolamunnage-Dona R, Parry CM, Pirmohamed M. Calprotectin and lactoferrin faecal levels in patients with Clostridium difficile infection (CDI): a prospective cohort study. PLoS One. 2014 Aug 29;9(8):e106118. doi: 10.1371/journal.pone.0106118. eCollection 2014.
PMID: 25170963
citation: Kim J, Kim H, Oh HJ, Kim HS, Hwang YJ, Yong D, Jeong SH, Lee K. Fecal Calprotectin Level Reflects the Severity of Clostridium difficile Infection. Ann Lab Med. 2017 Jan;37(1):53-57. doi: 10.3343/alm.2017.37.1.53.
PMID: 27834066
citation: Peretz A, Tkhawkho L, Pastukh N, Brodsky D, Halevi CN, Nitzan O. Correlation between fecal calprotectin levels, disease severity and the hypervirulent ribotype 027 strain in patients with Clostridium difficile infection. BMC Infect Dis. 2016 Jun 22;16:309. doi: 10.1186/s12879-016-1618-8.
PMID: 27334992
responsible party type: Principal Investigator
investigator affiliation: Mahidol University
investigator full name: Julajak Limsrivilai
investigator title: Assist.Professor
mesh term: Diarrhea
sharing ipd: No
provided document: 