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

Phase 2

Terminated

• Conditions: Hypertension
• Interventions: Drug: Sirolimus

• Registration Number: NCT01709136
• Lead Sponsor: University of Pittsburgh

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.

Study Timeline

• Study Start: 2005-12
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Study First Submitted: 2010-06-29
• Study First Submitted QC: 2012-10-16
• Study First Posted: 2012-10-17
• Results First Submitted: 2016-01-14
• Results First Submitted QC: 2016-03-21
• Results First Posted: 2016-04-21
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-29
• Last Update Posted: 2023-03-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sirolimus	Sirolimus	-

Primary Outcome Measures

Name	Time	Method
Early and Late Pharmacokinetics of Sirolimus (SRL)	1 year	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

Name	Time	Method
SRL Can Substitute TAC	12 months	Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function
SRL Prevent TAC-related Side Effects	1 year	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)
PK Parameters for Tacrolimus and Sirolimus	12 months	pharmacokinetics (PK) of SRL after a single dose and after steady state has been achieved; and the pharmacokinetics of tacrolimus once at steady state