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

Hypertension Clinical Trial

— Sirolimus  

Official title:

Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Early Nephrotoxicity and/or Hypertension Due to Tacrolimus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01709136
• Other study ID #: 07100379
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: December 2005
• Est. completion date: January 2010

Study information

• Verified date: March 2023
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pharmacokinetics of Tacrolimus and Sirolimus alone and in combination in liver transplant recipients.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Pittsburgh

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 year
Secondary	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	12 months
Secondary	SRL Can Substitute TAC	Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function	12 months
Secondary	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)	1 year