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

NCT ID: NCT01709136

Last Updated: 2023-03-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2010-01-31

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.

Conditions

Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sirolimus

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

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.

Interventions

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'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.

Intervention Type: DRUG

Other Intervention Names

Sirolimus (Rapamycin); Tacrolimus (FK506)

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Rakesh Sindhi

Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rakesh Sindhi

Role: PRINCIPAL_INVESTIGATOR

UPitt

Other Identifiers

07100379

Identifier Type: -

Identifier Source: org_study_id