<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/NCT03252925</url>
  </required_header>
  <id_info>
    <org_study_id>SOOCHOW-HY-2017</org_study_id>
    <nct_id>NCT03252925</nct_id>
  </id_info>
  <brief_title>A Safety and Efficacy Study of NAC in Patients With TA-TMA</brief_title>
  <official_title>A Safety and Efficacy Study of N-acetylcysteine in Patients With Transplant-Associated Thrombotic Microangiopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Affiliated Hospital of Soochow University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The First Affiliated Hospital of Soochow University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      HSCT associated thrombotic microangiopathy(TA-TMA) is a heterogeneous, fatal disorder seen&#xD;
      within 100 days post-transplant and presents with thrombocytopenia, hemolysis, acute renal&#xD;
      failure, mental status changes and involvement of other organs. N-Acetylcysteine (NAC) is a&#xD;
      small, simple molecule that began as a generic drug almost 40 years ago. It has since been&#xD;
      approved by the FDA for many indications. The investigators conducted an prospective clinical&#xD;
      trial to evaluate the safety and efficiency of NAC in patients with TA-TMA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hematopoietic stem cell transplantation (HSCT) has been commonly used as a potentially&#xD;
      curative option in the treatment of various hematological malignancies. However, it may end&#xD;
      up with serious complications in various systems, including the hemostatic system. HSCT&#xD;
      associated thrombotic microangiopathy(TA-TMA) is a heterogeneous, fatal disorder seen within&#xD;
      100 days post-transplant and presents with thrombocytopenia, hemolysis, acute renal failure,&#xD;
      mental status changes and involvement of other organs. Since the pathophysiology has not been&#xD;
      clarified, there are no established treatments for TA-TMA several agents seem to have&#xD;
      successful results. N-Acetylcysteine (NAC) is a small, simple molecule that began as a&#xD;
      generic drug almost 40 years ago. It has since been approved by the FDA for many indications.&#xD;
      Studies showed NAC reduce plasma VWF multimers and VWF multimeric size without an effect on&#xD;
      the bleeding time in vitro and in vivo, thus proposed as a possible supplementary treatment&#xD;
      for TTP. The investigators conducted an prospective clinical trial to evaluate the safety and&#xD;
      efficiency of NAC in patients with TA-TMA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2017</start_date>
  <completion_date type="Actual">October 1, 2021</completion_date>
  <primary_completion_date type="Actual">October 1, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Incidence of TA-TMA.</measure>
    <time_frame>100 days</time_frame>
    <description>The incidence of TMA after HSCT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Level of VWF Multimers</measure>
    <time_frame>100 days</time_frame>
    <description>The level of VWF multimers in patients post HSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Level of Endothelial Micro Particle</measure>
    <time_frame>100 days</time_frame>
    <description>The level of endothelial micro particle in patients post HSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Level of TNF-α</measure>
    <time_frame>40 days</time_frame>
    <description>The level of TNF-α in patients post HSCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Level of ROS</measure>
    <time_frame>100 days</time_frame>
    <description>The level of ROS in patients post HSCT.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">170</enrollment>
  <condition>Thrombotic Microangiopathies</condition>
  <condition>Hematologic Diseases</condition>
  <arm_group>
    <arm_group_label>Experimental Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>N-Acetylcysteine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Oral Tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-Acetylcysteine</intervention_name>
    <description>50mg/Kg.d, oral</description>
    <arm_group_label>Experimental Group</arm_group_label>
    <other_name>NAC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>50mg/Kg.d, oral</description>
    <arm_group_label>Control Group</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients be scheduled to undergo HSCT;&#xD;
&#xD;
          2. Not received decitabine 6 month ago;&#xD;
&#xD;
          3. Without severe organ damage;&#xD;
&#xD;
          4. ECOG 0-2;&#xD;
&#xD;
          5. Informed consent were obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Be sensitive to NAC;&#xD;
&#xD;
          2. Bronchial asthma；&#xD;
&#xD;
          3. Peptic ulcer；&#xD;
&#xD;
          4. Severe organ damage；&#xD;
&#xD;
          5. Pregnancy and breastfeeding women；&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Depei Wu, MD. PhD.</last_name>
    <role>Study Chair</role>
    <affiliation>The First Affiliated Hospital of Soochow University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First affiliated Hospital of SooChow University</name>
      <address>
        <city>Suzhou</city>
        <state>Jiangsu</state>
        <zip>215006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>George JN, Lopez JA, Konkle BA. N-Acetylcysteine: an old drug, a new insight, a potentially effective treatment for thrombotic thrombocytopenic purpura. Transfusion. 2014 May;54(5):1205-7. doi: 10.1111/trf.12561. No abstract available.</citation>
    <PMID>24819072</PMID>
  </reference>
  <reference>
    <citation>Tersteeg C, Roodt J, Van Rensburg WJ, Dekimpe C, Vandeputte N, Pareyn I, Vandenbulcke A, Plaimauer B, Lamprecht S, Deckmyn H, Lopez JA, De Meyer SF, Vanhoorelbeke K. N-acetylcysteine in preclinical mouse and baboon models of thrombotic thrombocytopenic purpura. Blood. 2017 Feb 23;129(8):1030-1038. doi: 10.1182/blood-2016-09-738856. Epub 2016 Dec 23.</citation>
    <PMID>28011677</PMID>
  </reference>
  <reference>
    <citation>Acedillo RR, Govind M, Kashgary A, Clark WF. Treatment of severe, refractory and rapidly evolving thrombotic thrombocytopenic purpura. BMJ Case Rep. 2016 Jun 9;2016:bcr2016215491. doi: 10.1136/bcr-2016-215491.</citation>
    <PMID>27284100</PMID>
  </reference>
  <reference>
    <citation>Rottenstreich A, Hochberg-Klein S, Rund D, Kalish Y. The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura. J Thromb Thrombolysis. 2016 May;41(4):678-83. doi: 10.1007/s11239-015-1259-6.</citation>
    <PMID>26245827</PMID>
  </reference>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>May 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <results_first_submitted>January 3, 2022</results_first_submitted>
  <results_first_submitted_qc>January 19, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">February 14, 2022</results_first_posted>
  <last_update_submitted>January 19, 2022</last_update_submitted>
  <last_update_submitted_qc>January 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>N-acetylcysteine</keyword>
  <keyword>Complement</keyword>
  <keyword>Thrombotic Microangiopathies</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vascular Diseases</mesh_term>
    <mesh_term>Hematologic Diseases</mesh_term>
    <mesh_term>Thrombotic Microangiopathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 1, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT03252925/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Experimental Group</title>
          <description>N-Acetylcysteine&#xD;
N-Acetylcysteine: 50mg/Kg.d, oral</description>
        </group>
        <group group_id="P2">
          <title>Control Group</title>
          <description>Placebo Oral Tablet&#xD;
Placebo Oral Tablet: 50mg/Kg.d, oral</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="80"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="74"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NAC Group</title>
          <description>N-Acetylcysteine 50mg/Kg.d, oral</description>
        </group>
        <group group_id="B2">
          <title>Placebo Group</title>
          <description>Placebo oral tablet 50mg/Kg.d, oral</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="66"/>
            <count group_id="B2" value="74"/>
            <count group_id="B3" value="140"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="122"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Yellow Race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                    <measurement group_id="B2" value="74"/>
                    <measurement group_id="B3" value="140"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                    <measurement group_id="B2" value="74"/>
                    <measurement group_id="B3" value="140"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary Diseases</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Acute myeloid leukemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Acute lymphoblastic leukemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aplastic anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chronic myelogenous leukemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Myelodysplastic syndrome</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphoma and multiple myeloma</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Transplant Type</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>HLA identical sibling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Related haplo-identical</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Matched unrelated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Incidence of TA-TMA.</title>
        <description>The incidence of TMA after HSCT.</description>
        <time_frame>100 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NAC Group</title>
            <description>N-Acetylcysteine 50mg/Kg.d, oral</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Placebo Oral Tablet 50mg/Kg.d, oral</description>
          </group>
        </group_list>
        <measure>
          <title>The Incidence of TA-TMA.</title>
          <description>The incidence of TMA after HSCT.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Level of VWF Multimers</title>
        <description>The level of VWF multimers in patients post HSCT.</description>
        <time_frame>100 days</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Level of Endothelial Micro Particle</title>
        <description>The level of endothelial micro particle in patients post HSCT.</description>
        <time_frame>100 days</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Level of TNF-α</title>
        <description>The level of TNF-α in patients post HSCT.</description>
        <time_frame>40 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>NAC Group</title>
            <description>N-Acetylcysteine 50mg/Kg.d, oral</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Placebo Oral Tablet 50mg/Kg.d, oral</description>
          </group>
        </group_list>
        <measure>
          <title>The Level of TNF-α</title>
          <description>The level of TNF-α in patients post HSCT.</description>
          <units>pg/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" lower_limit="0" upper_limit="1.4"/>
                    <measurement group_id="O2" value="0.3" lower_limit="0" upper_limit="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Level of ROS</title>
        <description>The level of ROS in patients post HSCT.</description>
        <time_frame>100 days</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>100 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>NAC Group</title>
          <description>N-Acetylcysteine 50mg/Kg.d, oral</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo Oral Tablet 50mg/Kg.d, oral</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="74"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="74"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="59" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="72" subjects_at_risk="74"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="74"/>
              </event>
              <event>
                <sub_title>Erythra</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="74"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain or diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="49" subjects_at_risk="74"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal complications</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="74"/>
              </event>
              <event>
                <sub_title>Gastrointestinal bleeding</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="74"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="74"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hemorrhagic cystitis</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="43" subjects_at_risk="74"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough or expectoration</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="74"/>
              </event>
              <event>
                <sub_title>Chest tightness</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="74"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness or headache</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="74"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Several outcome indicators are entirely inconsistent with our study's actual course of execution. First, the occurrence of TA-TMA was not limited to the first 100 days after hematopoietic stem cell transplantation. Secondly, the detection of VWF multimers, endothelial microparticles, and ROS was not performed according to the protocol.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Yue Han</name_or_title>
      <organization>The First Affiliated Hospital of Soochow University</organization>
      <phone>13901551669</phone>
      <email>hanyue@suda.edu.cn</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03252925
org study id: SOOCHOW-HY-2017
nct id: NCT03252925
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
HSCT associated thrombotic microangiopathy(TA-TMA) is a heterogeneous, fatal disorder seen
      within 100 days post-transplant and presents with thrombocytopenia, hemolysis, acute renal
      failure, mental status changes and involvement of other organs. N-Acetylcysteine (NAC) is a
      small, simple molecule that began as a generic drug almost 40 years ago. It has since been
      approved by the FDA for many indications. The investigators conducted an prospective clinical
      trial to evaluate the safety and efficiency of NAC in patients with TA-TMA.
Hematopoietic stem cell transplantation (HSCT) has been commonly used as a potentially
      curative option in the treatment of various hematological malignancies. However, it may end
      up with serious complications in various systems, including the hemostatic system. HSCT
      associated thrombotic microangiopathy(TA-TMA) is a heterogeneous, fatal disorder seen within
      100 days post-transplant and presents with thrombocytopenia, hemolysis, acute renal failure,
      mental status changes and involvement of other organs. Since the pathophysiology has not been
      clarified, there are no established treatments for TA-TMA several agents seem to have
      successful results. N-Acetylcysteine (NAC) is a small, simple molecule that began as a
      generic drug almost 40 years ago. It has since been approved by the FDA for many indications.
      Studies showed NAC reduce plasma VWF multimers and VWF multimeric size without an effect on
      the bleeding time in vitro and in vivo, thus proposed as a possible supplementary treatment
      for TTP. The investigators conducted an prospective clinical trial to evaluate the safety and
      efficiency of NAC in patients with TA-TMA.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: The Incidence of TA-TMA.
time frame: 100 days
description: The incidence of TMA after HSCT.
measure: The Level of VWF Multimers
time frame: 100 days
description: The level of VWF multimers in patients post HSCT.
measure: The Level of Endothelial Micro Particle
time frame: 100 days
description: The level of endothelial micro particle in patients post HSCT.
measure: The Level of TNF-α
time frame: 40 days
description: The level of TNF-α in patients post HSCT.
measure: The Level of ROS
time frame: 100 days
description: The level of ROS in patients post HSCT.
arm group label: Experimental Group
arm group type: Experimental
description: N-Acetylcysteine
arm group label: Control Group
arm group type: Placebo Comparator
description: Placebo Oral Tablet
intervention type: Drug
intervention name: N-Acetylcysteine
description: 50mg/Kg.d, oral
arm group label: Experimental Group
other name: NAC
intervention type: Drug
intervention name: Placebo Oral Tablet
description: 50mg/Kg.d, oral
arm group label: Control Group
other name: Placebo
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Depei Wu, MD. PhD.
role: Study Chair
affiliation: The First Affiliated Hospital of Soochow University
facility: 
country: China
citation: George JN, Lopez JA, Konkle BA. N-Acetylcysteine: an old drug, a new insight, a potentially effective treatment for thrombotic thrombocytopenic purpura. Transfusion. 2014 May;54(5):1205-7. doi: 10.1111/trf.12561. No abstract available.
PMID: 24819072
citation: Tersteeg C, Roodt J, Van Rensburg WJ, Dekimpe C, Vandeputte N, Pareyn I, Vandenbulcke A, Plaimauer B, Lamprecht S, Deckmyn H, Lopez JA, De Meyer SF, Vanhoorelbeke K. N-acetylcysteine in preclinical mouse and baboon models of thrombotic thrombocytopenic purpura. Blood. 2017 Feb 23;129(8):1030-1038. doi: 10.1182/blood-2016-09-738856. Epub 2016 Dec 23.
PMID: 28011677
citation: Acedillo RR, Govind M, Kashgary A, Clark WF. Treatment of severe, refractory and rapidly evolving thrombotic thrombocytopenic purpura. BMJ Case Rep. 2016 Jun 9;2016:bcr2016215491. doi: 10.1136/bcr-2016-215491.
PMID: 27284100
citation: Rottenstreich A, Hochberg-Klein S, Rund D, Kalish Y. The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura. J Thromb Thrombolysis. 2016 May;41(4):678-83. doi: 10.1007/s11239-015-1259-6.
PMID: 26245827
responsible party type: Sponsor
mesh term: Vascular Diseases
mesh term: Hematologic Diseases
mesh term: Thrombotic Microangiopathies
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Several outcome indicators are entirely inconsistent with our study's actual course of execution. First, the occurrence of TA-TMA was not limited to the first 100 days after hematopoietic stem cell transplantation. Secondly, the detection of VWF multimers, endothelial microparticles, and ROS was not performed according to the protocol.
point of contact: 