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

Neurotoxicity Clinical Trial

Official title:

Sirolimus Switching From Calcinurin Inhibitors (CNI) 90 - 180 Days After Liver Transplantation

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00834496
• Other study ID #: 08D.12
• Status: Withdrawn
• Phase: N/A
• First received: January 30, 2009
• Last updated: January 11, 2017
• Start date: January 2009
• Est. completion date: January 2010

Study information

• Verified date: January 2017
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hepatic Fibrosis on Biopsy
• Neurotoxicity
• Neurotoxicity Syndromes
• Post Transplant Diabetes
• Renal Toxicity
• Side Effects of Calcineurin Inhibitors

Intervention

Procedure:
• Liver biopsy
percutaneous liver biopsy

Locations

Country	Name	City	State
United States	THomas Jefferson University and Hospital	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Thomas Jefferson University	Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		12 months	No