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Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Tacrolimus Toxicity (Sirolimus)

Primary Purpose

Hypertension

Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Sirolimus
Sponsored by
University of Pittsburgh
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Recipients of primary liver (cadaver/liver, whole/segmental) transplants 5- 30 years old.
  • Rejection-free post-transplant course for at least 3 months
  • Renal dysfunction (15% decrease in age-adjusted calculated creatinine clearance)
  • Hypertension requiring anti-hypertensive mediations.
  • Informed consent.
  • Weight ≥15 kg.

Exclusion Criteria:

  • Rejection or infections within 3 months of enrollment.
  • Intent to continue TAC
  • Active participation in ongoing studies of immunosuppressive agents.
  • Lack of informed consent.
  • Pregnant or breast feeding
  • HIV positive

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Sirolimus

    Arm Description

    Outcomes

    Primary Outcome Measures

    Early and Late Pharmacokinetics of Sirolimus (SRL)
    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.

    Secondary Outcome Measures

    PK Parameters for Tacrolimus and Sirolimus
    pharmacokinetics (PK) of SRL after a single dose and after steady state has been achieved; and the pharmacokinetics of tacrolimus once at steady state
    SRL Can Substitute TAC
    Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function
    SRL Prevent TAC-related Side Effects
    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)

    Full Information

    First Posted
    June 29, 2010
    Last Updated
    March 29, 2023
    Sponsor
    University of Pittsburgh
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01709136
    Brief Title
    Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Tacrolimus Toxicity
    Acronym
    Sirolimus
    Official Title
    Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Early Nephrotoxicity and/or Hypertension Due to Tacrolimus
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Terminated
    Why Stopped
    Sirolimus usage discontinued since black box warning
    Study Start Date
    December 2005 (undefined)
    Primary Completion Date
    January 2010 (Actual)
    Study Completion Date
    January 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Pittsburgh

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Pharmacokinetics of Tacrolimus and Sirolimus alone and in combination in liver transplant recipients.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hypertension

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    3 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Sirolimus
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Sirolimus
    Other Intervention Name(s)
    Sirolimus (Rapamycin), Tacrolimus (FK506)
    Intervention 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.
    Primary Outcome Measure Information:
    Title
    Early and Late Pharmacokinetics of Sirolimus (SRL)
    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.
    Time Frame
    1 year
    Secondary Outcome Measure Information:
    Title
    PK Parameters for Tacrolimus and Sirolimus
    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
    Time Frame
    12 months
    Title
    SRL Can Substitute TAC
    Description
    Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function
    Time Frame
    12 months
    Title
    SRL Prevent TAC-related Side Effects
    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)
    Time Frame
    1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Year
    Maximum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Recipients of primary liver (cadaver/liver, whole/segmental) transplants 5- 30 years old. Rejection-free post-transplant course for at least 3 months Renal dysfunction (15% decrease in age-adjusted calculated creatinine clearance) Hypertension requiring anti-hypertensive mediations. Informed consent. Weight ≥15 kg. Exclusion Criteria: Rejection or infections within 3 months of enrollment. Intent to continue TAC Active participation in ongoing studies of immunosuppressive agents. Lack of informed consent. Pregnant or breast feeding HIV positive
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Rakesh Sindhi
    Organizational Affiliation
    UPitt
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Tacrolimus Toxicity

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