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

About this trial
This is an interventional treatment trial for Hypertension
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
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
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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