<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/NCT03283176</url>
  </required_header>
  <id_info>
    <org_study_id>Haematological Prof. in DAAs</org_study_id>
    <nct_id>NCT03283176</nct_id>
  </id_info>
  <brief_title>Hematologic Profile, Vit. B12 and Folic Acid in Cirrhotics Received Sofosbuvir and Daclatasvir With or Without Ribavirin</brief_title>
  <official_title>Changes in Hematologic Profile, Vitamin B12 and Folic Acid Level in Cirrhotic Patients Received Sofosbuvir and Daclatasvir With or Without Ribavirin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Use of Ribavirin could affect hematologic profile of the patients negatively. With advent of&#xD;
      new antiviral therapy, the preexisting hematologic changes may alter or corrected after&#xD;
      treatment. However, this point is still not properly studied.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hepatitis C virus (HCV) infection is a global health problem that affects 170 million people&#xD;
      worldwide, and approximately 55% (95 million) of the infected population is in South East&#xD;
      Asia and Western Pacific countries.&#xD;
&#xD;
      Hepatitis C virus (HCV) is considered one of the main causes of chronic hepatitis and also&#xD;
      may be complicated by serious complications as liver cirrhosis, ascites and hepatocellular&#xD;
      carcinoma. It is also, one of the leading indications for liver transplantation (LT) in&#xD;
      adults around the world.&#xD;
&#xD;
      Abnormalities in hematological parameters are common in patients with cirrhosis. The&#xD;
      pathogenesis of abnormal hematological indices (HIs) in cirrhosis is multifactorial and&#xD;
      includes portal hypertension-induced sequestration, alterations in bone marrow stimulating&#xD;
      factors, viral- and toxin-induced bone marrow suppression and consumption or loss.&#xD;
      Abnormalities in HIs are associated with an increased risk of complications including&#xD;
      bleeding and infection.&#xD;
&#xD;
      So, early recognition and early treatment of those patients with chronic HCV infection can&#xD;
      modify its natural history. There are many factors affecting the outcome of HCV infection as&#xD;
      viral, environmental and host factors, including immunologic and genetic susceptibilities.&#xD;
&#xD;
      Till 2011, the main lines of therapy were Interferon plus ribavirin for at least 48 weeks but&#xD;
      these combinations was associated with low incidence of Sustained Virological Response (SVR).&#xD;
      Now, there is era of Direct Acting Analogues that used for treatment of patients with chronic&#xD;
      HCV infection and associated with high rate of SVR.&#xD;
&#xD;
      Daclatasvir is a first-in-class HCV NS5A replication complex inhibitor, and Sofosbuvir is a&#xD;
      nucleotide analogue HCV NS5B polymerase inhibitor. Both have potent antiviral activity and&#xD;
      broad genotypic coverage and are administered orally once daily.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Actual">January 14, 2020</completion_date>
  <primary_completion_date type="Actual">March 1, 2019</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>Vitamin B12</measure>
    <time_frame>1 year</time_frame>
    <description>By ELISA Technique, in Pg/ml</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Folic Acid</measure>
    <time_frame>1 year</time_frame>
    <description>By ELISA technique, in Pg/ml</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">50</enrollment>
  <condition>Liver Cirrhoses</condition>
  <condition>Chronic Hepatitis c</condition>
  <condition>Directly Acting Antivirals</condition>
  <arm_group>
    <arm_group_label>Sofo-Dacla with Ribavirin</arm_group_label>
    <description>Chronic Hepatitis C related Liver Cirrhosis patients who will take sofosbuveir, Daclatasvir with Ribavirin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sofo-Dacla without Ribavirin</arm_group_label>
    <description>Chronic Hepatitis C related Liver Cirrhosis patients who will take sofosbuveir, Daclatasvir without Ribavirin</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Vitamin B12 and Folic Acid</intervention_name>
    <description>Vitamin B12 and Folic Acid measurement by ELISA technique</description>
    <arm_group_label>Sofo-Dacla with Ribavirin</arm_group_label>
    <arm_group_label>Sofo-Dacla without Ribavirin</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Fifty patients were diagnosed to have HCV-related liver cirrhosis and candidate for anti-&#xD;
        HCV therapy&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients known to have HCV-related liver cirrhosis and candidate for therapy with&#xD;
             Sofosbuvir and Daclatasvir with or without Ribavirin&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic hepatitis due causes other than chronic HCV infection&#xD;
&#xD;
          -  Coinfection with HIV or HBV infection&#xD;
&#xD;
          -  Hepatocellular carcinoma&#xD;
&#xD;
          -  Decompensated cirrhosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>Mohamed Shaban Redwan Helal</name>
      <address>
        <city>Assiut</city>
        <zip>71111</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009 Apr;49(4):1335-74. doi: 10.1002/hep.22759. No abstract available.</citation>
    <PMID>19330875</PMID>
  </reference>
  <reference>
    <citation>Promrat K, McDermott DH, Gonzalez CM, Kleiner DE, Koziol DE, Lessie M, Merrell M, Soza A, Heller T, Ghany M, Park Y, Alter HJ, Hoofnagle JH, Murphy PM, Liang TJ. Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C. Gastroenterology. 2003 Feb;124(2):352-60. doi: 10.1053/gast.2003.50061. Erratum In: Gastroenterology. 2003 Apr;124(4):1168.</citation>
    <PMID>12557141</PMID>
  </reference>
  <reference>
    <citation>Lam AM, Espiritu C, Bansal S, Micolochick Steuer HM, Niu C, Zennou V, Keilman M, Zhu Y, Lan S, Otto MJ, Furman PA. Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus. Antimicrob Agents Chemother. 2012 Jun;56(6):3359-68. doi: 10.1128/AAC.00054-12. Epub 2012 Mar 19.</citation>
    <PMID>22430955</PMID>
  </reference>
  <reference>
    <citation>Ampuero J, Romero-Gomez M, Reddy KR. Review article: HCV genotype 3 - the new treatment challenge. Aliment Pharmacol Ther. 2014 Apr;39(7):686-98. doi: 10.1111/apt.12646.</citation>
    <PMID>24612116</PMID>
  </reference>
  <reference>
    <citation>Qamar AA, Grace ND. Abnormal hematological indices in cirrhosis. Can J Gastroenterol. 2009 Jun;23(6):441-5. doi: 10.1155/2009/591317.</citation>
    <PMID>19543577</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>October 14, 2020</last_update_submitted>
  <last_update_submitted_qc>October 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Mohammed Shaaban Redwan Helal</investigator_full_name>
    <investigator_title>Resident doctor at Tropical Medicine and Gastroenterology Department</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Folic Acid</mesh_term>
    <mesh_term>Vitamin B 12</mesh_term>
    <mesh_term>Hydroxocobalamin</mesh_term>
  </intervention_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/NCT03283176
org study id: Haematological Prof. in DAAs
nct id: NCT03283176
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Use of Ribavirin could affect hematologic profile of the patients negatively. With advent of
      new antiviral therapy, the preexisting hematologic changes may alter or corrected after
      treatment. However, this point is still not properly studied.
Hepatitis C virus (HCV) infection is a global health problem that affects 170 million people
      worldwide, and approximately 55% (95 million) of the infected population is in South East
      Asia and Western Pacific countries.

      Hepatitis C virus (HCV) is considered one of the main causes of chronic hepatitis and also
      may be complicated by serious complications as liver cirrhosis, ascites and hepatocellular
      carcinoma. It is also, one of the leading indications for liver transplantation (LT) in
      adults around the world.

      Abnormalities in hematological parameters are common in patients with cirrhosis. The
      pathogenesis of abnormal hematological indices (HIs) in cirrhosis is multifactorial and
      includes portal hypertension-induced sequestration, alterations in bone marrow stimulating
      factors, viral- and toxin-induced bone marrow suppression and consumption or loss.
      Abnormalities in HIs are associated with an increased risk of complications including
      bleeding and infection.

      So, early recognition and early treatment of those patients with chronic HCV infection can
      modify its natural history. There are many factors affecting the outcome of HCV infection as
      viral, environmental and host factors, including immunologic and genetic susceptibilities.

      Till 2011, the main lines of therapy were Interferon plus ribavirin for at least 48 weeks but
      these combinations was associated with low incidence of Sustained Virological Response (SVR).
      Now, there is era of Direct Acting Analogues that used for treatment of patients with chronic
      HCV infection and associated with high rate of SVR.

      Daclatasvir is a first-in-class HCV NS5A replication complex inhibitor, and Sofosbuvir is a
      nucleotide analogue HCV NS5B polymerase inhibitor. Both have potent antiviral activity and
      broad genotypic coverage and are administered orally once daily.
observational model: Cohort
time perspective: Prospective
measure: Vitamin B12
time frame: 1 year
description: By ELISA Technique, in Pg/ml
measure: Folic Acid
time frame: 1 year
description: By ELISA technique, in Pg/ml
arm group label: Sofo-Dacla with Ribavirin
description: Chronic Hepatitis C related Liver Cirrhosis patients who will take sofosbuveir, Daclatasvir with Ribavirin
arm group label: Sofo-Dacla without Ribavirin
description: Chronic Hepatitis C related Liver Cirrhosis patients who will take sofosbuveir, Daclatasvir without Ribavirin
intervention type: Diagnostic Test
intervention name: Vitamin B12 and Folic Acid
description: Vitamin B12 and Folic Acid measurement by ELISA technique
arm group label: Sofo-Dacla with Ribavirin
arm group label: Sofo-Dacla without Ribavirin
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
facility: 
country: Egypt
citation: Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009 Apr;49(4):1335-74. doi: 10.1002/hep.22759. No abstract available.
PMID: 19330875
citation: Promrat K, McDermott DH, Gonzalez CM, Kleiner DE, Koziol DE, Lessie M, Merrell M, Soza A, Heller T, Ghany M, Park Y, Alter HJ, Hoofnagle JH, Murphy PM, Liang TJ. Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C. Gastroenterology. 2003 Feb;124(2):352-60. doi: 10.1053/gast.2003.50061. Erratum In: Gastroenterology. 2003 Apr;124(4):1168.
PMID: 12557141
citation: Lam AM, Espiritu C, Bansal S, Micolochick Steuer HM, Niu C, Zennou V, Keilman M, Zhu Y, Lan S, Otto MJ, Furman PA. Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus. Antimicrob Agents Chemother. 2012 Jun;56(6):3359-68. doi: 10.1128/AAC.00054-12. Epub 2012 Mar 19.
PMID: 22430955
citation: Ampuero J, Romero-Gomez M, Reddy KR. Review article: HCV genotype 3 - the new treatment challenge. Aliment Pharmacol Ther. 2014 Apr;39(7):686-98. doi: 10.1111/apt.12646.
PMID: 24612116
citation: Qamar AA, Grace ND. Abnormal hematological indices in cirrhosis. Can J Gastroenterol. 2009 Jun;23(6):441-5. doi: 10.1155/2009/591317.
PMID: 19543577
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Mohammed Shaaban Redwan Helal
investigator title: Resident doctor at Tropical Medicine and Gastroenterology Department
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Liver Cirrhosis
mesh term: Folic Acid
mesh term: Vitamin B 12
mesh term: Hydroxocobalamin
sharing ipd: No