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

NCT01709136 | Terminated Phase 2 Results DMC

• 1 other identifier: 07100379
• Study Type: interventional
• Target: 3
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• PK Parameters for Tacrolimus and Sirolimus

  12 months

• SRL Can Substitute TAC

  12 months

• SRL Prevent TAC-related Side Effects

  1 year

Study Arms (1)

Sirolimus

EXPERIMENTAL

Drug: Sirolimus

Interventions

Sirolimus 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.

Also known as: Sirolimus (Rapamycin), Tacrolimus (FK506)

Sirolimus

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pittsburgh: lead

MeSH Terms

Conditions

Hypertension

Interventions

Sirolimus; Tacrolimus

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Complete follow-up failed, due to early study termination as a result of FDA black box warning (6/11/2009) about Sirolimus in liver transplant recipients (risk of thrombosis and death).

Results Point of Contact

• Title: Dr. Rakesh Sindhi, MD
• Organization: Children's Hospital of Pittsburgh

rakesh.sindhi@chp.edu

412-692-6110

Study Officials

• Rakesh Sindhi

  UPitt

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: June 29, 2010
• First Posted: October 17, 2012
• Study Start: December 1, 2005
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: March 30, 2023
• Results First Posted: April 21, 2016

Record last verified: 2023-03