Study Comparing in Livertransplantation Recipients With Tacrolimus Alone Versus Tacrolimus&Sirolimus

NCT01958190 | Completed Phase 4

• 1 other identifier: LOL-III-1
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 3

Brief Summary

In this study we compare long term renal function in liver transplantation recipients treated with standard dose extended-release tacrolimus alone and recipients treated with a combination of low dose extended-release tacrolimus and low dose sirolimus. The hypothesis is that the patients treated with the combination have better long term renal function than the patients treated with standard dose tacrolimus alone.

Conditions

Liver Disease

Keywords

Liver transplantation long term renal function; tacrolimus sirolimus

Outcome Measures

Primary Outcomes (1)

• Renal function

  Percentage of patients with cGFR \< 60ml/min

  3 years

Secondary Outcomes (2)

• Malignancies

  3 years

• Diabetes Mellitus

  3 years

Study Arms (2)

Tacrolimus

ACTIVE COMPARATOR

Patient received standard-dose of Tracrolimus Advagraf (5-10 ng/ml) and 7.5 mg prednison; lower or discontinue steroids after day 180 at the discretion of the treating physician

Drug: Tacrolimus

combination Tacrolimus and Sirolimus

EXPERIMENTAL

Patients receive combination of low-dose extended release Tacrolimus and low-dose Sirolimus

Drug: Tacrolimus and Sirolimus

Interventions

Tacrolimus and Sirolimus DRUG

Arm 1 once daily combination therapy of normal dosed extended-release tacrolimus and prednisone for 3 months and monotherapy once daily extended-release tacrolimus thereafter up to 3 years after liver transplantation. Arm 2 once daily combination therapy of low doses sirolimus and extended-release tacrolimus and prednisone for 3 months and combination therapy of low dose sirolimus and extended-release tacrolimus thereafter for up to 3 years after liver transplantation Continue Advagraf (5-10 ng/ml) and 7.5 mg prednison; lower or discontinue steroids after day 180 at the discretion of the treating physician Conversion to sirolimus (3-5 ng/ml) and decrease Advagraf (3-5 ng/ml); 7.5 mg prednisone and lower or discontinue steroids after day 180 at the discretion of the treating physician

Also known as: Advagraf [Astellas Pharma bv), Rapamune

combination Tacrolimus and Sirolimus

Tacrolimus DRUG

Patient received standard-dose of Tracrolimus Advagraf (5-10 ng/ml) and 7.5 mg prednison; lower or discontinue steroids after day 180 at the discretion of the treating physician

Also known as: Advagraf

Tacrolimus

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary liver transplantation or retransplantation within 14 days after first transplantation
• Use of Advagraf at least 2 weeks prior to randomization
• Patent hepatic artery
• Closed abdominal wound
• Stable graft function
• Positive informed consent at time of randomization
• Age 18-70 years

You may not qualify if:

• Treatment with investigational drugs within 3 months before start of therapy
• Multi organ transplantation
• cGFR \< 30 ml/min
• Proteinuria \> 800 mg/24 h
• Hyperlipidemia refractory to optimal medical management (Cholesterol \> 9 mmol/l and/or triglycerides \> 8.5 mmol/l). Patients with controlled hyperlipidemia are acceptable at the time of randomization.
• Known hypersensitivity to sirolimus or its derivatives
• Thrombocytes \< 50 x 109 /L
• Leukocytes \< 2.5 x 109 /L
• Haemoglobin \< 6 mmol/L
• Biopsy proven rejection 2 weeks prior to randomization
• HIV positivity
• Signs of recurrent or de novo cancer
• Patients with non-HCC malignancies within the past 5 years (excluding successfully treated squamous cell carcinoma and basal cell carcinoma of the skin)
• Evidence of significant local or systemic infection
• Pregnancy or breast feeding

Sponsors & Collaborators

• Foundation for Liver Research: lead

Study Sites (3)

UMCG

Groningen, 9713 GZ, Netherlands

Location

LUMC

Leiden, 2333 ZA, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015CE, Netherlands

Location

MeSH Terms

Conditions

Liver Diseases

Interventions

Tacrolimus; Sirolimus

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Herold J Metselaar, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2013
• First Posted: October 9, 2013
• Study Start: February 7, 2011
• Primary Completion: May 20, 2021
• Study Completion: May 20, 2021
• Last Updated: March 18, 2022

Record last verified: 2022-03

Locations

NL (3)