Preservation of Renal Function in Liver Transplant Recipients With Certican Therapy

NCT ID: NCT00378014

Last Updated: 2015-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 276 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2013-01-31

Brief Summary

The study is designed to show that everolimus initiation together with reduction and thereafter discontinuation of calcineurin inhibitor (CNI) will improve significantly renal function in de novo liver transplant recipients as compared to continuation of CNI-based treatment.

Conditions

Liver Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus

Basiliximab plus everolimus-based immunosuppressive regimen following the reduction and cessation of initial CNI regimen plus optional steroids according to local best practice

Group Type: EXPERIMENTAL

basiliximab

Intervention Type: DRUG

All patients who met the eligibility criteria were treated with 2 doses of basiliximab on Day 0 (transplantation) and Day 4.

CNI

Intervention Type: DRUG

Patients who met the screening eligibility received CNI-based immunosuppressive therapy for 1 month. Then at week 4 (or week 8 at maximum), patients randomized to the CNI arm continued on CNI-based immunosuppressive therapy.

Calcineurin Inhibitor (CNI)

Basiliximab plus CNI-based immunosuppressive regimen according to local best practice plus optional steroids according to local best practice

Group Type: ACTIVE_COMPARATOR

everolimus

Intervention Type: DRUG

Start dose of everolimus was 1.5 mg in the morning followed by 1.5 mg in the evening. After one week, the dose was adjusted to achieve trough levels between 5-12 ng/mL. Once trough levels were above 5ng/mL, the CNI dose was reduced to 70%. At week 8 post-baseline (latest at week 16 post baseline), CNI was completely discontinued. For patients receiving Ciclosporin A (CiA) as CNI, the everolimus dosage was adjusted to achieve a trough level of 8-12 ng/mL, prior to discontinuation of CiA. After discontinuation of CNI, everolimus was maintained at a trough level of 5-12 ng/mL.

basiliximab

Intervention Type: DRUG

All patients who met the eligibility criteria were treated with 2 doses of basiliximab on Day 0 (transplantation) and Day 4.

CNI

Intervention Type: DRUG

Patients who met the screening eligibility received CNI-based immunosuppressive therapy for 1 month. Then at week 4 (or week 8 at maximum), patients randomized to the CNI arm continued on CNI-based immunosuppressive therapy.

Interventions

everolimus

Start dose of everolimus was 1.5 mg in the morning followed by 1.5 mg in the evening. After one week, the dose was adjusted to achieve trough levels between 5-12 ng/mL. Once trough levels were above 5ng/mL, the CNI dose was reduced to 70%. At week 8 post-baseline (latest at week 16 post baseline), CNI was completely discontinued. For patients receiving Ciclosporin A (CiA) as CNI, the everolimus dosage was adjusted to achieve a trough level of 8-12 ng/mL, prior to discontinuation of CiA. After discontinuation of CNI, everolimus was maintained at a trough level of 5-12 ng/mL.

Intervention Type: DRUG

basiliximab

All patients who met the eligibility criteria were treated with 2 doses of basiliximab on Day 0 (transplantation) and Day 4.

Intervention Type: DRUG

CNI

Patients who met the screening eligibility received CNI-based immunosuppressive therapy for 1 month. Then at week 4 (or week 8 at maximum), patients randomized to the CNI arm continued on CNI-based immunosuppressive therapy.

Intervention Type: DRUG

Other Intervention Names

certican; simulect

Eligibility Criteria

Inclusion Criteria

• Males or females 18 - 70 years old
• Liver transplant recipient (living or deceased donor)
• Patients in whom an allograft biopsy will not be contraindicated

Exclusion Criteria

• Recipients of multiple solid organ transplants or patients that have already received a transplant in the past
• HCV positive patients who need an active anti-viral treatment (HCV- positive patients without active antiviral treatment are allowed)
• HIV positive patients
• Patients who are breast feeding
• Patients with a current severe systemic infection
• Presence of any hypersensitivity to drugs similar to Certican® (e.g. macrolides)
• Preexisting (i.e. not related to CNI-damage) renal dysfunction that, according to the judgment of the investigator, will not significantly improve after transplantation (i.e., for example, patients that are expected to have a cGFR below 50ml/min at 4 weeks post transplantation)
• Patients that have received Simulect prior to this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Innsbruck, , Austria

Novartis Investigative Site

Vienna, , Austria

Novartis Investigative Site

Berlin, Germany, Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Jena, , Germany

Novartis Investigative Site

Münster, , Germany

Novartis Investigative Site

Regensburg, , Germany

Novartis Investigative Site

Tübingen, , Germany

Novartis Investigative Site

Groningen, , Netherlands

Novartis Investigative Site

Rotterdam, , Netherlands

Novartis Investigative Site

Zurich, Switzerland, Switzerland

Novartis Investigative Site

Geneva, , Switzerland

Countries

Austria; Germany; Netherlands; Switzerland

Other Identifiers

2005-002920-32

Identifier Type: -

Identifier Source: secondary_id

CRAD001HDE10

Identifier Type: -

Identifier Source: org_study_id