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

This study has been terminated.
(Sirolimus usage discontinued since black box warning)
Sponsor:
Information provided by (Responsible Party):
Rakesh Sindhi, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01709136
First received: June 29, 2010
Last updated: March 21, 2016
Last verified: March 2016
  Purpose
Pharmacokinetics of Tacrolimus and Sirolimus alone and in combination in liver transplant recipients.

Condition Intervention Phase
Hypertension
Drug: Sirolimus
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetics of Sirolimus and Tacrolimus in Liver Transplant Recipients With Early Nephrotoxicity and/or Hypertension Due to Tacrolimus

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Early and Late Pharmacokinetics of Sirolimus (SRL) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Whether Sirolimus can substitute Tacrolimus in the stable post-transplant state, without compromising allograft function

  • SRL Prevent TAC-related Side Effects [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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)


Enrollment: 3
Study Start Date: December 2005
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sirolimus 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.
Other Names:
  • Sirolimus (Rapamycin)
  • Tacrolimus (FK506)

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.
  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709136

Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Rakesh Sindhi UPitt
  More Information

Responsible Party: Rakesh Sindhi, Professor of Surgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01709136     History of Changes
Other Study ID Numbers: 07100379 
Study First Received: June 29, 2010
Results First Received: January 14, 2016
Last Updated: March 21, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Tacrolimus
Sirolimus
Everolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on July 24, 2016