xml: <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/NCT06040684</url>
    </required_header>
    <id_info>
      <org_study_id>INT-01-HLATX-Kidney</org_study_id>
      <secondary_id>15/RVO-FNOs/2018</secondary_id>
      <nct_id>NCT06040684</nct_id>
    </id_info>
    <brief_title>Development of Antibodies Against Transplant Kidney After Infection</brief_title>
    <official_title>Development of Antibodies Against Transplant Kidney After Infection</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital Ostrava</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital Ostrava</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>
        Kidney transplantation is the best method of renal replacement in patients with irreversible&#xD;
        renal failure. One of the biggest problems today is premature loss of function of the&#xD;
        transplanted kidney. This occurs most often on the basis of chronic humoral rejection. This&#xD;
        is the immune response to the kidney, in which the specific antibodies play a crucial role&#xD;
        (both against the HLA and the non-HLA system).&#xD;
  &#xD;
        The aim of this study is to analyze one of the situations where the production of antibodies&#xD;
        can begin to occur. This is a serious acute infection (bacterial, viral, or fungal), where it&#xD;
        is necessary to significantly reduce doses of immunosuppressives. At the time of reduced&#xD;
        immunosuppression, the immune system can recognize the transplanted kidney as foreign to the&#xD;
        human body and begin to fight against it.&#xD;
  &#xD;
        In this study, the investigators will monitor antibodies against the transplanted kidney in&#xD;
        patients with severe acute infection. A serious infection in this study is one that requires&#xD;
        acute hospitalization and reduced doses of immunosuppressive drugs. The researchers will&#xD;
        measure the antibodies in the blood upon admission and then in 5 weeks.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Kidney transplantation significantly improves the prognosis and quality of life of patients&#xD;
        with irreversible renal failure (end-stage kidney disease), requiring hemodialysis or&#xD;
        peritoneal dialysis. The length of the function of the transplanted kidney depends on a&#xD;
        number of factors. One of the most significant deterioration factors and subsequent graft&#xD;
        function failure, in the long run, is the production of antibodies against HLA as well as&#xD;
        transplant antigens that lead to acute or chronic humoral rejection. Chronic humoral&#xD;
        rejection leading to transplant glomerulopathy is the most common cause of loss of function&#xD;
        of the transplanted kidney. Treatment interventions in this area are still ineffective.&#xD;
  &#xD;
        In spite of immunosuppressive therapy, some patients develop anti-transplant antibodies (both&#xD;
        against HLA and non-HLA antibody molecules) even with stable graft function. However, these&#xD;
        patients have an increased risk of losing their function due to chronic humoral rejection.&#xD;
        The HLA-DR and HLA-DQ molecules have the greatest immunogenicity.&#xD;
  &#xD;
        Patients after kidney transplantation may have many complications. Both surgical (vascular&#xD;
        anastomoses stenoses, wound healing problems, graft vascular thromboses, lymphocele, urinary&#xD;
        leakage) and non-surgical, some of which are immune-compromised (rejection) and others,&#xD;
        result from the mechanism of action of immunosuppressive preparations (infections,&#xD;
        cardiovascular effects). Amongst potentially life-threatening conditions include acute&#xD;
        infections. Immunosuppressed infections have their own specifics. In addition to the&#xD;
        increased risk of infections; also a different spectrum of possible originators is known. It&#xD;
        is also possible to encounter opportunistic infections - pneumocystis, cytomegalovirus,&#xD;
        polyomavirus infections. Another specific feature is often a different course of infection -&#xD;
        patients may not have significantly expressed clinical or laboratory findings and may&#xD;
        progress rapidly. For these reasons, physicians are often forced to significantly reduce&#xD;
        immunosuppression rates in patients with acute infection, despite the increased risk of&#xD;
        developing rejection. This situation increases the risk of initiation by both cell-mediated&#xD;
        rejection and antibody-mediated rejection. Signs of rejection are very nonspecific and the&#xD;
        only diagnostic method is graft biopsy. Previous studies have shown that the production of&#xD;
        antibodies to the transplanted kidney is preceded by clinical signs of deterioration in graft&#xD;
        function over weeks to months. Patients included in the study according to the criteria will&#xD;
        be examined for the presence of HLA antibodies and non-HLA on admission (within 48 hours of&#xD;
        admission) and 5 weeks after the first sample method LUMINEX xMAP.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">August 1, 2018</start_date>
    <completion_date type="Actual">December 31, 2021</completion_date>
    <primary_completion_date type="Actual">November 30, 2021</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Production of HLA and nonHLA antibodies - Luminex</measure>
      <time_frame>42 months</time_frame>
      <description>Screening for HLA and nonHLA antibodies by Luminex. The test result will be positive (MFI - mean fluorescence intensity above 300) or negative.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Analysis of antibody formation according to age</measure>
      <time_frame>42 months</time_frame>
      <description>The formation of antibodies will be analysed according to the age of the patients in years.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Analysis of antibody formation according to time from transplantation</measure>
      <time_frame>42 months</time_frame>
      <description>The formation of antibodies will be analysed according to the time from transplantation in months.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Creatinine value</measure>
      <time_frame>42 months</time_frame>
      <description>The baseline kidney function will be assessed (according to the KDIGO organization) The kidney will be classified as a normal function, 1st, 2nd, 3rd according to the creatinine value).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Input Inflammatory Parameters - CRP (C-reactive protein)</measure>
      <time_frame>42 months</time_frame>
      <description>The input inflammatory parameters will be assessed (CRP (mg/l).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Input Inflammatory Parameters - IL-6 (Interleukin-6)</measure>
      <time_frame>42 months</time_frame>
      <description>The input inflammatory parameters will be assessed (IL-6 (ng/l).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of HLA mismatches during transplant (0-6)</measure>
      <time_frame>42 months</time_frame>
      <description>The number of HLA mismatches during transplant (0-6) will be recorded.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Length of immunosuppression reduction</measure>
      <time_frame>42 months</time_frame>
      <description>The length of immunosuppression reduction will be analysed in 3 categories - up to 5 days, 5-10 days and over 10 days.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Delayed graft function after transplantation</measure>
      <time_frame>42 months</time_frame>
      <description>The delayed graft function after transplantation will be assessed in 2 categories - YES / NO -as a need for haemodialysis in the first week after transplantation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Long-term graft function</measure>
      <time_frame>42 months</time_frame>
      <description>The long-term graft function will be assessed by the last early graft function (eGF) in ml / sec- 3 categories - normal function, G1-2 and G3-5 by KDIGO.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Type of infection</measure>
      <time_frame>42 months</time_frame>
      <description>The type of infection observed in the patients will be assessed and recorded - urinary, respiratory, other - determined by the doctor when the patient is discharged.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Presence of antibodies</measure>
      <time_frame>42 months</time_frame>
      <description>The presence of antibodies (YES/NO) will be determined in patients using the LUMINEX method - antibody value using MFI - mean fluorescence intensity.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EGF value</measure>
      <time_frame>42 months</time_frame>
      <description>The function of the transplanted kidney will be assessed at 6 months (+ -14 days) from the first measurement assessing the EGF value (ml/sec)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proteinuria</measure>
      <time_frame>42 months</time_frame>
      <description>The function of the transplanted kidney will be assessed at 6 months (+ -14 days) from the first measurement assessing the proteinuria (g/l)</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Actual">30</enrollment>
    <condition>Acute Infection</condition>
    <condition>Kidney Failure</condition>
    <arm_group>
      <arm_group_label>Level of antibodies in kidney transplant recipients</arm_group_label>
      <description>Patients with kidney transplant with a severe acute infection will be enrolled in the study. Levels of antibodies in these patients will be analyzed.</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Level of antibodies</intervention_name>
      <description>The level of antibodies against transplanted kidney in patients with a severe acute infection will be measured upon admission and then in 5 weeks.</description>
      <arm_group_label>Level of antibodies in kidney transplant recipients</arm_group_label>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Antibodies in blood samples (excessive material remaining after performing all necessary&#xD;
        standard diagnostic tests) will be analyzed upon admission and then in 5 weeks.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Kidney transplant recipients with acute infection (viral, bacterial or fungal) requiring&#xD;
          acute inpatient care&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 18 years and over.&#xD;
  &#xD;
            -  A kidney transplant patient - from a living donor or from a cadaveric donor (donor&#xD;
               after circulatory or brain death). The patient will be included after 1st transplant&#xD;
               and possible retransplantation.&#xD;
  &#xD;
            -  The patient is hospitalized or newly admitted to the FN Ostrava internal clinic for&#xD;
               acute infection + requires the reduction of immunosuppressive therapy (dose reduction&#xD;
               or discontinuation of any of the maintenance immunosuppressive preparations -&#xD;
               tacrolimus, cyclosporin A, sirolimus, everolimus, azathioprine, mycophenolate).&#xD;
  &#xD;
            -  Acute infection (to be admitted to an internal clinic - determine the time of&#xD;
               admission or the time of the first symptom of infection in the already hospitalized)&#xD;
               occurred at least more than 48 hours after transplantation (from reperfusion time) and&#xD;
               a maximum of 10 years after transplantation.&#xD;
  &#xD;
            -  The patient did not receive intravenous immunoglobulins within the last 24 hours prior&#xD;
               to first sampling.&#xD;
  &#xD;
            -  This is not a pregnant woman.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patient's death before the 2nd blood sampling.&#xD;
  &#xD;
            -  The patient condition was conclusively determined as something other than acute&#xD;
               infection (acute rejection episode, acute pancreatitis, malignant tumor, ...).&#xD;
               Unfamiliarity with localization of the infection or its origin, assuming an infectious&#xD;
               etiology, is NOT an exclusion criterion.&#xD;
  &#xD;
            -  The patient was graftectomized - removal of the transplanted kidney, between the 1st&#xD;
               and 2nd antibody determination.&#xD;
  &#xD;
            -  Detection of pregnancy when the term of conception is calculated before the 2nd&#xD;
               antibody count.&#xD;
  &#xD;
            -  One or more transfusions of the erythrocytes or plasma between the 1st and 2nd&#xD;
               measurements were administered to the patient.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Zdeněk Lys, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Hospital Ostrava</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>University Hospital Ostrava</name>
        <address>
          <city>Ostrava</city>
          <state>Moravian-Silesian Region</state>
          <zip>708 52</zip>
          <country>Czechia</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Czechia</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>May 23, 2018</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>kidney transplant</keyword>
    <keyword>HLA antibodies</keyword>
    <keyword>acute infection</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Infections</mesh_term>
      <mesh_term>Communicable Diseases</mesh_term>
      <mesh_term>Renal Insufficiency</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Antibodies</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>The investigators do not plan to make individual participant data available to other researchers.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06040684
  org study id: INT-01-HLATX-Kidney
  secondary id: 15/RVO-FNOs/2018
  nct id: NCT06040684
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Kidney transplantation is the best method of renal replacement in patients with irreversible
        renal failure. One of the biggest problems today is premature loss of function of the
        transplanted kidney. This occurs most often on the basis of chronic humoral rejection. This
        is the immune response to the kidney, in which the specific antibodies play a crucial role
        (both against the HLA and the non-HLA system).
  
        The aim of this study is to analyze one of the situations where the production of antibodies
        can begin to occur. This is a serious acute infection (bacterial, viral, or fungal), where it
        is necessary to significantly reduce doses of immunosuppressives. At the time of reduced
        immunosuppression, the immune system can recognize the transplanted kidney as foreign to the
        human body and begin to fight against it.
  
        In this study, the investigators will monitor antibodies against the transplanted kidney in
        patients with severe acute infection. A serious infection in this study is one that requires
        acute hospitalization and reduced doses of immunosuppressive drugs. The researchers will
        measure the antibodies in the blood upon admission and then in 5 weeks.
  Kidney transplantation significantly improves the prognosis and quality of life of patients
        with irreversible renal failure (end-stage kidney disease), requiring hemodialysis or
        peritoneal dialysis. The length of the function of the transplanted kidney depends on a
        number of factors. One of the most significant deterioration factors and subsequent graft
        function failure, in the long run, is the production of antibodies against HLA as well as
        transplant antigens that lead to acute or chronic humoral rejection. Chronic humoral
        rejection leading to transplant glomerulopathy is the most common cause of loss of function
        of the transplanted kidney. Treatment interventions in this area are still ineffective.
  
        In spite of immunosuppressive therapy, some patients develop anti-transplant antibodies (both
        against HLA and non-HLA antibody molecules) even with stable graft function. However, these
        patients have an increased risk of losing their function due to chronic humoral rejection.
        The HLA-DR and HLA-DQ molecules have the greatest immunogenicity.
  
        Patients after kidney transplantation may have many complications. Both surgical (vascular
        anastomoses stenoses, wound healing problems, graft vascular thromboses, lymphocele, urinary
        leakage) and non-surgical, some of which are immune-compromised (rejection) and others,
        result from the mechanism of action of immunosuppressive preparations (infections,
        cardiovascular effects). Amongst potentially life-threatening conditions include acute
        infections. Immunosuppressed infections have their own specifics. In addition to the
        increased risk of infections; also a different spectrum of possible originators is known. It
        is also possible to encounter opportunistic infections - pneumocystis, cytomegalovirus,
        polyomavirus infections. Another specific feature is often a different course of infection -
        patients may not have significantly expressed clinical or laboratory findings and may
        progress rapidly. For these reasons, physicians are often forced to significantly reduce
        immunosuppression rates in patients with acute infection, despite the increased risk of
        developing rejection. This situation increases the risk of initiation by both cell-mediated
        rejection and antibody-mediated rejection. Signs of rejection are very nonspecific and the
        only diagnostic method is graft biopsy. Previous studies have shown that the production of
        antibodies to the transplanted kidney is preceded by clinical signs of deterioration in graft
        function over weeks to months. Patients included in the study according to the criteria will
        be examined for the presence of HLA antibodies and non-HLA on admission (within 48 hours of
        admission) and 5 weeks after the first sample method LUMINEX xMAP.
  observational model: Case-Only
  time perspective: Prospective
  measure: Production of HLA and nonHLA antibodies - Luminex
  time frame: 42 months
  description: Screening for HLA and nonHLA antibodies by Luminex. The test result will be positive (MFI - mean fluorescence intensity above 300) or negative.
  measure: Analysis of antibody formation according to age
  time frame: 42 months
  description: The formation of antibodies will be analysed according to the age of the patients in years.
  measure: Analysis of antibody formation according to time from transplantation
  time frame: 42 months
  description: The formation of antibodies will be analysed according to the time from transplantation in months.
  measure: Creatinine value
  time frame: 42 months
  description: The baseline kidney function will be assessed (according to the KDIGO organization) The kidney will be classified as a normal function, 1st, 2nd, 3rd according to the creatinine value).
  measure: Input Inflammatory Parameters - CRP (C-reactive protein)
  time frame: 42 months
  description: The input inflammatory parameters will be assessed (CRP (mg/l).
  measure: Input Inflammatory Parameters - IL-6 (Interleukin-6)
  time frame: 42 months
  description: The input inflammatory parameters will be assessed (IL-6 (ng/l).
  measure: Number of HLA mismatches during transplant (0-6)
  time frame: 42 months
  description: The number of HLA mismatches during transplant (0-6) will be recorded.
  measure: Length of immunosuppression reduction
  time frame: 42 months
  description: The length of immunosuppression reduction will be analysed in 3 categories - up to 5 days, 5-10 days and over 10 days.
  measure: Delayed graft function after transplantation
  time frame: 42 months
  description: The delayed graft function after transplantation will be assessed in 2 categories - YES / NO -as a need for haemodialysis in the first week after transplantation.
  measure: Long-term graft function
  time frame: 42 months
  description: The long-term graft function will be assessed by the last early graft function (eGF) in ml / sec- 3 categories - normal function, G1-2 and G3-5 by KDIGO.
  measure: Type of infection
  time frame: 42 months
  description: The type of infection observed in the patients will be assessed and recorded - urinary, respiratory, other - determined by the doctor when the patient is discharged.
  measure: Presence of antibodies
  time frame: 42 months
  description: The presence of antibodies (YES/NO) will be determined in patients using the LUMINEX method - antibody value using MFI - mean fluorescence intensity.
  measure: EGF value
  time frame: 42 months
  description: The function of the transplanted kidney will be assessed at 6 months (+ -14 days) from the first measurement assessing the EGF value (ml/sec)
  measure: Proteinuria
  time frame: 42 months
  description: The function of the transplanted kidney will be assessed at 6 months (+ -14 days) from the first measurement assessing the proteinuria (g/l)
  arm group label: Level of antibodies in kidney transplant recipients
  description: Patients with kidney transplant with a severe acute infection will be enrolled in the study. Levels of antibodies in these patients will be analyzed.
  intervention type: Diagnostic Test
  intervention name: Level of antibodies
  description: The level of antibodies against transplanted kidney in patients with a severe acute infection will be measured upon admission and then in 5 weeks.
  arm group label: Level of antibodies in kidney transplant recipients
  Antibodies in blood samples (excessive material remaining after performing all necessary
        standard diagnostic tests) will be analyzed upon admission and then in 5 weeks.
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Zdeněk Lys, MD
  role: Principal Investigator
  affiliation: University Hospital Ostrava
  facility: 
  country: Czechia
  responsible party type: Sponsor
  mesh term: Infections
  mesh term: Communicable Diseases
  mesh term: Renal Insufficiency
  mesh term: Antibodies
  sharing ipd: No
  ipd description: The investigators do not plan to make individual participant data available to other researchers.