Preservation of Renal Function in Liver Transplant Recipients With Certican Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00378014
First received: September 15, 2006
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Liver Transplantation
Drug: everolimus
Drug: basiliximab
Drug: CNI
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Presentation of Renal Function in Liver Transplant Recipients With Certican Therapy: PROTECT Study A Twelve-month, Multicenter, Randomized, Open-label Study of Safety, Tolerability and Efficacy of Certican-based Regimen Versus Calcineurin Inhibitor-based Regimen in de Novo Liver Transplant Recipients

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Calculated Glomerular Filtration Rate (cGFR) [ Time Frame: Month 11 ] [ Designated as safety issue: No ]
    This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.


Secondary Outcome Measures:
  • Incidence of Efficacy Failure [ Time Frame: Month 11 ] [ Designated as safety issue: No ]
    Efficacy failure was defined as the composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, death, lost to follow-up (from any reason), whichever occurred first. Incidence of efficacy failure was estimated using crude rate estimation (relative frequency).

  • Incidence of the Need for a Change in the Immunosuppressive Regimen [ Time Frame: Month 11 ] [ Designated as safety issue: No ]
    The incidence of any changes in the immunosuppressive regimen other than allowed in the study protocol (for example, introduction of Mycophenolic acid (MPA) or sirolimus) was estimated using crude rate estimation (relative frequency).

  • Incidence of Renal Deterioration [ Time Frame: Baseline, Month 11 ] [ Designated as safety issue: No ]
    Renal deterioration was defined as a decrease by ≥25% in the cGFR compared to baseline and confirmed by one consecutive measurement. The analysis of this outcome measure was omitted because of missing relevance.

  • Renal Function (cGFR) [ Time Frame: Month 5 ] [ Designated as safety issue: No ]
    This outcome measure evaluated renal function by assessing the calculated GFR based on the Cockcroft-Gault formula.

  • Incidence of Treated BPAR [ Time Frame: Month 11 ] [ Designated as safety issue: No ]
    The incidence of treated BPAR was estimated using crude rate estimation (relative frequency).

  • Patient and Graft Survival [ Time Frame: Month 11 ] [ Designated as safety issue: No ]
    Patient survival was defined as the time from date of randomization to date of death from any cause. If a patient was not known to have died, patient survival was censored as the date of last contact. Graft survival was defined as the time from the date of randomization to the date of graft loss. If a patient was not known to suffer from a graft loss or died without graft loss, time to graft loss was censored with date of last contact or date of death, respectively. Patient and graft survival were analyzed using the Kaplan Meier method.

  • Hepatitis C Virus (HCV) Replication in HCV-positive Patients [ Time Frame: Baseline, Month 5 ] [ Designated as safety issue: No ]
    HCV ribonucleic acid (RNA) was measured by real time reverse transcriptase polymerase chain reaction (PCR; copies per mL).

  • Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death [ Time Frame: From randomization to Month 11 ] [ Designated as safety issue: Yes ]
    Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.

  • Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death [ Time Frame: Month 12 to Month 59 post-baseline ] [ Designated as safety issue: Yes ]
    Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.


Enrollment: 276
Study Start Date: August 2006
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus
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
All patients who met the eligibility criteria were treated with 2 doses of basiliximab on Day 0 (transplantation) and Day 4.
Other Name: simulect
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.
Active Comparator: Calcineurin Inhibitor (CNI)
Basiliximab plus CNI-based immunosuppressive regimen according to local best practice plus optional steroids according to local best practice
Drug: 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.
Other Name: certican
Drug: basiliximab
All patients who met the eligibility criteria were treated with 2 doses of basiliximab on Day 0 (transplantation) and Day 4.
Other Name: simulect
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • Other protocol-defined inclusion/exclusion criteria may apply.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378014

Locations
Austria
Novartis Investigative Site
Innsbruck, Austria, A-6020
Novartis Investigative Site
Wien, Austria, A-1090
Germany
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Frankfurt, Germany, 60590
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Jena, Germany, 07740
Novartis Investigative Site
Muenster, Germany, 48149
Novartis Investigative Site
Regensburg, Germany, 93053
Novartis Investigative Site
Tübingen, Germany, 72076
Netherlands
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Novartis Investigative Site
Rotterdam, Netherlands, 3015 CE
Switzerland
Novartis Investigative Site
Genève, Switzerland, 1211
Novartis Investigative Site
Zurich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00378014     History of Changes
Other Study ID Numbers: CRAD001HDE10, 2005-002920-32
Study First Received: September 15, 2006
Results First Received: January 16, 2014
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by Novartis:
Liver transplantation, everolimus, CNI

Additional relevant MeSH terms:
Immunosuppressive Agents
Everolimus
Sirolimus
Basiliximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 28, 2014