Preservation of Renal Function in Liver Transplant Recipients With Certican Therapy

NCT00378014 | Completed Phase 3 Results DMC

• 2 other identifiers: CRAD001HDE102005-002920-32
• Study Type: interventional
• Target: 276
• Locations: 4 countries
• Sites: 16

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

Keywords

Liver transplantation, everolimus, CNI

Outcome Measures

Primary Outcomes (1)

• Calculated Glomerular Filtration Rate (cGFR)

  This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.

  Month 11

Secondary Outcomes (9)

• Incidence of Efficacy Failure

  Month 11

• Incidence of the Need for a Change in the Immunosuppressive Regimen

  Month 11

• Incidence of Renal Deterioration

  Baseline, Month 11

• Renal Function (cGFR)

  Month 5

• Incidence of Treated BPAR

  Month 11

Study Arms (2)

Everolimus

EXPERIMENTAL

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

Drug: basiliximab; Drug: CNI

Calcineurin Inhibitor (CNI)

ACTIVE COMPARATOR

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

Drug: everolimus; Drug: basiliximab; Drug: CNI

Interventions

everolimus 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.

Also known as: certican

Calcineurin Inhibitor (CNI)

basiliximab DRUG

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

Also known as: simulect

Calcineurin Inhibitor (CNI); Everolimus

CNI 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); Everolimus

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (16)

Novartis Investigative Site

Innsbruck, A-6020, Austria

Location

Novartis Investigative Site

Vienna, A-1090, Austria

Location

Novartis Investigative Site

Berlin, Germany, 13353, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Jena, 07740, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Regensburg, 93053, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

Location

Novartis Investigative Site

Zurich, Switzerland, 8091, Switzerland

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

MeSH Terms

Interventions

Everolimus; Basiliximab

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2006
• First Posted: September 19, 2006
• Study Start: August 1, 2006
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: February 6, 2015
• Results First Posted: July 3, 2014

Record last verified: 2015-01

Locations

CH (2); NL (2); AU (2); DE (10)