Switching From One Type of Anti-rejection Drug (Tacrolimus or Cyclosporine) to Another (Sirolimus) Approximately 90-180 Days After Liver Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Thomas Jefferson University
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00834496
First received: January 30, 2009
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

Sirolimus can be safely switched as early as 90 days after liver transplantation with excellent tolerability and amelioration of the calcineurin inhibitor toxicity that initiated the switch.


Condition Intervention
Side Effects of Calcineurin Inhibitors
Renal Toxicity
Hepatic Fibrosis on Biopsy
Neurotoxicity
Post Transplant Diabetes
Procedure: Liver biopsy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Sirolimus Switching From Calcinurin Inhibitors (CNI) 90 - 180 Days After Liver Transplantation

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • The primary objective is that acute cellular rejection following a switch to sirolimus will be comparable to the historical rate at our center under calcineurin inhibitors of around 5% for post liver transplant recipients. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: January 2009
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1

Our experience with the use of Sirolimus is delineated below. About 15% to 20% of our patients are currently switched to Sirolimus.Indications for conversion from calcinurin inhibitors (CNIs) to Sirolimus more than 90 days post liver transplantation include:

  • CNI renal toxicity.
  • Hepatic fibrosis on biopsy.
  • CNI neurologic toxicity.
  • Post transplant diabetes. Any of the above 4 indications makes a patient a candidate for conversion from CNIs to Sirolimus at or > 90 days after liver transplantation.
Procedure: Liver biopsy
percutaneous liver biopsy

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

post liver transplant patients taking calcineurin inhibitors (tacrolimus or cyclosporine) as anti-reject medication

Criteria

Inclusion Criteria:

  1. Adult (18 years or older) patients undergoing liver transplantation at Thomas Jefferson University Hospital.
  2. Diagnosed with at least one of the following CNI side effects 90-180 days post transplantation:

    1. CNI renal toxicity. Any liver transplant recipient who has elevated creatinine level (greater than 1.4 mg/dl) and impaired creatinine clearance (MDRD) of 40-60 ml/minute or decreased by 15% compared to baseline in the setting of having a therapeutic CNI level, without suspicion of acute or chronic allograft rejection.
    2. Hepatic fibrosis on biopsy. Any patient who has fibrosis seen on liver biopsy with LFT's 2 times the upper normal limit.
    3. CNI neurologic toxicity. Any patient who has significant neurological side effects from CNIs. This will include the following: seizures not secondary to an epileptogenic focus or any metabolic derangement; alteration of speech ranging from aphasia to slurred speech; inability to be awake and alert.
    4. Post transplant diabetes. Any patient who has developed diabetes after transplant and in whom CNIs are thought to be contributing to poor glycemic control.
  3. Signed informed consent at approximately 90 -180 days post transplantation.

Exclusion Criteria:

  1. Invasive/surgical therapy within 2 weeks of the 90-180 day post transplantation conversion. (e.g. patients with T-tubes would not be eligible for the study because the T-tube removal will coincide with the conversion date).
  2. Open surgical wound at 90-180 days post transplantation.
  3. Acute cellular rejection during the first 90-180 days post transplantation.
  4. Re-transplants or multiple-organ transplants.
  5. Active infection.
  6. Pregnancy.
  7. Malignancy within 3 years prior to liver transplantation (except adequately treated basal cell carcinoma). Patients with HCC prior to transplant will not be excluded.
  8. Total cholesterol >300 mg/dl on medical treatment or triglycerides >150 mg/dl at 90-180 days post transplantation.
  9. White blood cell count <3,000/mm3 or platelet count <100,000/mm3 at 90-180 days post transplantation.
  10. Ascites.
  11. Patients on chemotherapy.
  12. Urine protein/creatinine ration > 0.5
  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: NCT00834496

Contacts
Contact: Cataldo Doria, MD, PhD 215-955-8920 cataldo.doria@jefferson.edu

Locations
United States, Pennsylvania
THomas Jefferson University and Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Silvia Vaccino-Salvadore, MBA    215-955-7744    silvia.vaccino@jefferson.edu   
Sponsors and Collaborators
Thomas Jefferson University
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Principal Investigator: Cataldo Doria, MD, PhD Thomas Jefferson University and Hospital
  More Information

No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00834496     History of Changes
Other Study ID Numbers: 08D.12
Study First Received: January 30, 2009
Last Updated: August 5, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neurotoxicity Syndromes
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014