<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/NCT01709136</url>
  </required_header>
  <id_info>
    <org_study_id>07100379</org_study_id>
    <nct_id>NCT01709136</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Tacrolimus Toxicity</brief_title>
  <acronym>Sirolimus</acronym>
  <official_title>Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Early Nephrotoxicity and/or Hypertension Due to Tacrolimus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pharmacokinetics of Tacrolimus and Sirolimus alone and in combination in liver transplant&#xD;
      recipients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Liver transplant patients receiving tacrolimus, and who experience side effects such as&#xD;
      hypertension and renal dysfunction, will be converted to sirolimus with low-dose tacrolimus,&#xD;
      or Tacrolimus withdrawal. This study will evaluate allograft function by serial clinical lab&#xD;
      testing, the pharmacokinetics of sirolimus and tacrolimus, the glomerular filtration rate&#xD;
      (GFR) and the potential side effect of sirolimus, such as marrow suppression and&#xD;
      hyperlipidemia. Two pharmacokinetic evaluations are planned: once around the third&#xD;
      post-transplant month and another one at about 12 months. Expected outcomes are, a better&#xD;
      understanding of sirolimus pharmacokinetic parameters over time in pediatric/adult liver&#xD;
      recipients and early efficacy and safety data of the sirolimus as a non-nephrotoxic&#xD;
      alternative to tacrolimus.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sirolimus usage discontinued since black box warning&#xD;
  </why_stopped>
  <start_date>December 2005</start_date>
  <completion_date type="Actual">January 2010</completion_date>
  <primary_completion_date type="Actual">January 2010</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Early and Late Pharmacokinetics of Sirolimus (SRL)</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate early and late pharmacokinetics of Sirolimus (SRL) , and safety and efficacy of conversion from tacrolimus (TAC) to sirolimus in liver transplant recipients who have been stable for at least 3 months, and who have early nephrotoxicity and/or hypertension due to use of tacrolimus.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK Parameters for Tacrolimus and Sirolimus</measure>
    <time_frame>12 months</time_frame>
    <description>pharmacokinetics (PK) of SRL after a single dose and after steady state has been achieved; and the pharmacokinetics of tacrolimus once at steady state</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SRL Can Substitute TAC</measure>
    <time_frame>12 months</time_frame>
    <description>Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SRL Prevent TAC-related Side Effects</measure>
    <time_frame>1 year</time_frame>
    <description>Whether SRL can prevent or minimize progression of selected TAC-related side-effects such as renal dysfunction as measured by clearance of iothalamate (Glomerular filtration rate &lt; 80 mL/min/1.73 m2) and hypertension (blood pressure &gt; 140/90 mm Hg)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Sirolimus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus</intervention_name>
    <description>Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the Children's Hospital of Pittsburgh's Pediatric Clinical and Translational Research Center (PCTRC) - See more at: http://www.chp.edu/research/our-facilities/pctrc, and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab. This phase can either be performed immediately after the 12-hour iothalamate GFR evaluation, or a few days later at the convenience of the subject.</description>
    <arm_group_label>Sirolimus</arm_group_label>
    <other_name>Sirolimus (Rapamycin)</other_name>
    <other_name>Tacrolimus (FK506)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Recipients of primary liver (cadaver/liver, whole/segmental) transplants 5- 30 years&#xD;
             old.&#xD;
&#xD;
          -  Rejection-free post-transplant course for at least 3 months&#xD;
&#xD;
          -  Renal dysfunction (15% decrease in age-adjusted calculated creatinine clearance)&#xD;
&#xD;
          -  Hypertension requiring anti-hypertensive mediations.&#xD;
&#xD;
          -  Informed consent.&#xD;
&#xD;
          -  Weight ≥15 kg.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Rejection or infections within 3 months of enrollment.&#xD;
&#xD;
          -  Intent to continue TAC&#xD;
&#xD;
          -  Active participation in ongoing studies of immunosuppressive agents.&#xD;
&#xD;
          -  Lack of informed consent.&#xD;
&#xD;
          -  Pregnant or breast feeding&#xD;
&#xD;
          -  HIV positive&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rakesh Sindhi</last_name>
    <role>Principal Investigator</role>
    <affiliation>UPitt</affiliation>
  </overall_official>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 29, 2010</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 17, 2012</study_first_posted>
  <results_first_submitted>January 14, 2016</results_first_submitted>
  <results_first_submitted_qc>March 21, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 21, 2016</results_first_posted>
  <last_update_submitted>March 29, 2023</last_update_submitted>
  <last_update_submitted_qc>March 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Rakesh Sindhi</investigator_full_name>
    <investigator_title>Professor of Surgery</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Temsirolimus</mesh_term>
    <mesh_term>MTOR Inhibitors</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sirolimus</title>
          <description>Sirolimus: Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the Children's Hospital of Pittsburgh Pediatric Clinical and Translational Research Center (PCTRC) - See more at: http://www.chp.edu/research/our-facilities/pctrc, and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab. This phase can either be performed immediately after the 12-hour iothalamate Glomerular Filtration Rate (GFR) evaluation, or a few days later at the convenience of the subject.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sirolimus</title>
          <description>Sirolimus: Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the PCTRC , and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab. This phase can either be performed immediately after the 12-hour iothalamate GFR evaluation, or a few days later at the convenience of the subject.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" 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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Secondary</type>
        <title>PK Parameters for Tacrolimus and Sirolimus</title>
        <description>pharmacokinetics (PK) of SRL after a single dose and after steady state has been achieved; and the pharmacokinetics of tacrolimus once at steady state</description>
        <time_frame>12 months</time_frame>
        <population>We were able to preform 3 pharmacokinetics (PK) profiles, one in each of three patients enrolled. However, due to emerging data and blackbox warnings from FDA suggesting that use of Sirolimus in liver transplant recipients be circumspect (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.</population>
        <group_list>
          <group group_id="O1">
            <title>Sirolimus</title>
            <description>Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the PCTRC , and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Parameters for Tacrolimus and Sirolimus</title>
          <description>pharmacokinetics (PK) of SRL after a single dose and after steady state has been achieved; and the pharmacokinetics of tacrolimus once at steady state</description>
          <population>We were able to preform 3 pharmacokinetics (PK) profiles, one in each of three patients enrolled. However, due to emerging data and blackbox warnings from FDA suggesting that use of Sirolimus in liver transplant recipients be circumspect (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>SRL Can Substitute TAC</title>
        <description>Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function</description>
        <time_frame>12 months</time_frame>
        <population>Due to FDA blackbox warnings (6/11/09) about Sirolimus in liver transplant recipients (risk of thrombosis and death), the study was terminated early. Due to the early termination of this study and small number of subjects enrolled (3), data analysis was not able to be completed.</population>
        <group_list>
          <group group_id="O1">
            <title>Sirolimus</title>
            <description>Sirolimus: Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the PCTRC , and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab..</description>
          </group>
        </group_list>
        <measure>
          <title>SRL Can Substitute TAC</title>
          <description>Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function</description>
          <population>Due to FDA blackbox warnings (6/11/09) about Sirolimus in liver transplant recipients (risk of thrombosis and death), the study was terminated early. Due to the early termination of this study and small number of subjects enrolled (3), data analysis was not able to be completed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Early and Late Pharmacokinetics of Sirolimus (SRL)</title>
        <description>To evaluate early and late pharmacokinetics of Sirolimus (SRL) , and safety and efficacy of conversion from tacrolimus (TAC) to sirolimus in liver transplant recipients who have been stable for at least 3 months, and who have early nephrotoxicity and/or hypertension due to use of tacrolimus.</description>
        <time_frame>1 year</time_frame>
        <population>Three pharmacokinetics (PK) profiles were performed, one in each of three patients who were enrolled. However, due to FDA blackbox warnings (6/11/2009) about Sirolimus in liver transplant recipients be circumspect (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.</population>
        <group_list>
          <group group_id="O1">
            <title>Sirolimus</title>
            <description>Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the PCTRC, and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab.</description>
          </group>
        </group_list>
        <measure>
          <title>Early and Late Pharmacokinetics of Sirolimus (SRL)</title>
          <description>To evaluate early and late pharmacokinetics of Sirolimus (SRL) , and safety and efficacy of conversion from tacrolimus (TAC) to sirolimus in liver transplant recipients who have been stable for at least 3 months, and who have early nephrotoxicity and/or hypertension due to use of tacrolimus.</description>
          <population>Three pharmacokinetics (PK) profiles were performed, one in each of three patients who were enrolled. However, due to FDA blackbox warnings (6/11/2009) about Sirolimus in liver transplant recipients be circumspect (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>SRL Prevent TAC-related Side Effects</title>
        <description>Whether SRL can prevent or minimize progression of selected TAC-related side-effects such as renal dysfunction as measured by clearance of iothalamate (Glomerular filtration rate &lt; 80 mL/min/1.73 m2) and hypertension (blood pressure &gt; 140/90 mm Hg)</description>
        <time_frame>1 year</time_frame>
        <population>Due to FDA blackbox warnings from FDA (6/11/2009) about Sirolimus in liver transplant recipients (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.</population>
        <group_list>
          <group group_id="O1">
            <title>Sirolimus</title>
            <description>Sirolimus: Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the PCTRC , and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab.</description>
          </group>
        </group_list>
        <measure>
          <title>SRL Prevent TAC-related Side Effects</title>
          <description>Whether SRL can prevent or minimize progression of selected TAC-related side-effects such as renal dysfunction as measured by clearance of iothalamate (Glomerular filtration rate &lt; 80 mL/min/1.73 m2) and hypertension (blood pressure &gt; 140/90 mm Hg)</description>
          <population>Due to FDA blackbox warnings from FDA (6/11/2009) about Sirolimus in liver transplant recipients (risk of thrombosis and death), the study was terminated early and data analysis was not able to be completed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <desc>There have been no adverse events or unanticipated events during the course of this study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Sirolimus</title>
          <description>Sirolimus: Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the PCTRC , and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab. This phase can either be performed immediately after the 12-hour iothalamate GFR evaluation, or a few days later at the convenience of the subject.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </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>Complete follow-up failed, due to early study termination as a result of FDA black box warning (6/11/2009) about Sirolimus in liver transplant recipients (risk of thrombosis and death).</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Rakesh Sindhi, MD</name_or_title>
      <organization>Children's Hospital of Pittsburgh</organization>
      <phone>412-692-6110</phone>
      <email>rakesh.sindhi@chp.edu</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/NCT01709136
org study id: 07100379
nct id: NCT01709136
lead sponsor: 
has dmc: Yes
Pharmacokinetics of Tacrolimus and Sirolimus alone and in combination in liver transplant
      recipients.
Liver transplant patients receiving tacrolimus, and who experience side effects such as
      hypertension and renal dysfunction, will be converted to sirolimus with low-dose tacrolimus,
      or Tacrolimus withdrawal. This study will evaluate allograft function by serial clinical lab
      testing, the pharmacokinetics of sirolimus and tacrolimus, the glomerular filtration rate
      (GFR) and the potential side effect of sirolimus, such as marrow suppression and
      hyperlipidemia. Two pharmacokinetic evaluations are planned: once around the third
      post-transplant month and another one at about 12 months. Expected outcomes are, a better
      understanding of sirolimus pharmacokinetic parameters over time in pediatric/adult liver
      recipients and early efficacy and safety data of the sirolimus as a non-nephrotoxic
      alternative to tacrolimus.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Early and Late Pharmacokinetics of Sirolimus (SRL)
time frame: 1 year
description: To evaluate early and late pharmacokinetics of Sirolimus (SRL) , and safety and efficacy of conversion from tacrolimus (TAC) to sirolimus in liver transplant recipients who have been stable for at least 3 months, and who have early nephrotoxicity and/or hypertension due to use of tacrolimus.
measure: PK Parameters for Tacrolimus and Sirolimus
time frame: 12 months
description: pharmacokinetics (PK) of SRL after a single dose and after steady state has been achieved; and the pharmacokinetics of tacrolimus once at steady state
measure: SRL Can Substitute TAC
time frame: 12 months
description: Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function
measure: SRL Prevent TAC-related Side Effects
time frame: 1 year
description: Whether SRL can prevent or minimize progression of selected TAC-related side-effects such as renal dysfunction as measured by clearance of iothalamate (Glomerular filtration rate < 80 mL/min/1.73 m2) and hypertension (blood pressure > 140/90 mm Hg)
arm group label: Sirolimus
arm group type: Experimental
intervention type: Drug
intervention name: Sirolimus
description: Single dose SRL pharmacokinetics and TAC steady state pharmacokinetics: This phase is applicable to both sets of patients: those with nephrotoxicity and those with hypertension. Patients will receive a single dose of SRL of 2 mg/m2. Blood sampling will be performed over a 24 hour stay in the Children's Hospital of Pittsburgh's Pediatric Clinical and Translational Research Center (PCTRC) - See more at: http://www.chp.edu/research/our-facilities/pctrc, and the sampling for 48 hour and 72 hour PK studies can be done at the outpatient lab. This phase can either be performed immediately after the 12-hour iothalamate GFR evaluation, or a few days later at the convenience of the subject.
arm group label: Sirolimus
other name: Sirolimus (Rapamycin)
other name: Tacrolimus (FK506)
criteria: 
gender: All
minimum age: 1 Year
maximum age: 18 Years
healthy volunteers: No
last name: Rakesh Sindhi
role: Principal Investigator
affiliation: UPitt
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Rakesh Sindhi
investigator title: Professor of Surgery
mesh term: Hypertension
mesh term: Sirolimus
mesh term: Temsirolimus
mesh term: MTOR Inhibitors
mesh term: Tacrolimus
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Complete follow-up failed, due to early study termination as a result of FDA black box warning (6/11/2009) about Sirolimus in liver transplant recipients (risk of thrombosis and death).
point of contact: 