Conversion From Sirolimus to Everolimus in the Maintenance Treatment of Liver Transplant Recipients

Conversion From Sirolimus to Everolimus in the Maintenance Treatment of Liver Transplant Recipients: A 1-year Observational Study

This study aims to determine the safety and efficacy of conversion of sirolimus to everolimus in the maintenance treatment of LT recipients. Patients will be monitored every 12 weeks after the switch of treatment for 48 weeks. The laboratory tests including hematological, renal, hepatic, and metabolic parameters will be performed at each visit. Twenty-four-hour urine creatinine clearance and proteinuria will be determined from a 24-hour urine collection at baseline and week 48.

Study Overview

• Status: Completed
• Conditions: Liver Transplant Recipients

Detailed Description

Everolimus (EVL) and sirolimus (SRL), an antagonist of mammalian target of rapamycin, has been introduced into solid organ transplantation to either replace or reduce the dose of potentially nephrotoxic calcineurin inhibitors. Although not approved for liver transplantation (LT), SRL has still been used in several LT centers. After EVL was approved by FDA and the Ministry of Health in Turkey for use in LT recipients, SRL was converted to EVL in our institution. This study aims to determine the safety and efficacy of conversion of SRL to EVL in the maintenance treatment of LT recipients.

Patients who switch from SRL to EVL will be monitored every 12 weeks after the switch of treatment for 48 weeks.

Efficacy measure will be included any observation in terms of biopsy-proven acute/chronic rejection and graft or patient loss due to rejection.

Safety evaluations will be included discontinuation of EVL and analyses of adverse events and grading laboratory abnormalities.

Laboratory evaluations will be included hematological (CBC), renal (serum creatinine, estimated glomerular filtration rate [eGFR; Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI)], and electrolytes), hepatic (serum transaminases, alkaline phosphatase, γ-glutamyl transferase, bilirubin, and albumin), and metabolic parameters (fasting glucose, cholesterol, and triglyceride) at each visit. Twenty-four-hour urine creatinine clearance and proteinuria will be determined from a 24-hour urine collection at baseline and week 48.

For patients who were on additional immunosuppressive treatments, those medications will also be continued.

• Study Type: Observational
• Enrollment (Actual): 66

Contacts and Locations

Study Locations

• Turkey
  • Izmir, Turkey, 35100
    • Ege University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants with liver transplantation who switch from sirolimus to everolimus

Description

Inclusion Criteria:

• Patients older than 18 years
• Liver transplant recipients who switch from sirolimus to everolimus

Exclusion Criteria:

• Patients who refuse the everolimus switching

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with advers events, biopsy-proven acute/chronic rejection, graft loss, or death from switching time to 48 weeks post-conversion.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laboratory follow-up (hematological)	It will include complete blood count (hemoglobin, hematocrit, leukocyte, and platelet)	At baseline and Weeks 12, 24, 36, and 48
Laboratory follow-up (hepatic)	It will include serum transaminases, alkaline phosphatase, γ-glutamyl transferase, bilirubin, and albumin	At baseline and Weeks 12, 24, 36, and 48
Laboratory follow-up (renal)	It will include serum creatinine, eGFR (MDRD and CKD-EPI), and electrolytes (sodium, potassium, calcium, magnesium, and phosphate)	At baseline and Weeks 12, 24, 36, and 48
Laboratory follow-up (metabolic)	It will include fasting glucose, cholesterol, and triglyceride.	At baseline and Weeks 12, 24, 36, and 48
Laboratory follow-up (24-hour urine creatinine clearance)		At baseline and Week 48
Laboratory follow-up (24-hour urine proteinuria)		At baseline and Week 48
Median dose of everolimus	The median dose of everolimus to reach the therapeutic range (3 - 8 ng/mL)	48 weeks

Collaborators and Investigators

• Sponsor: Ege University
• Investigators: Principal Investigator: Ilker Turan, M.D., Ege University

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: June 19, 2015
• First Submitted That Met QC Criteria: June 23, 2015
• First Posted (Estimate): June 26, 2015

Study Record Updates

• Last Update Posted (Estimate): December 21, 2016
• Last Update Submitted That Met QC Criteria: December 19, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Liver transplantation; Safety; Everolimus; Treatment outcome; Sirolimus
• Other Study ID Numbers: 15-3.1/53