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OpenTrials
Completed

NCT Number: NCT00378014

Preservation of Renal Function in Liver Transplant Recipients With Certican Therapy

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.

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Key information

Conditions

Liver Transplantation

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, Innsbruck, Austria

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Other names: certican

Basiliximab

Drug

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

Other names: simulect

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.

Primary outcomes

  1. Calculated Glomerular Filtration Rate (cGFR)

    Time frame: Month 11

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

Secondary outcomes

  1. Incidence of Efficacy Failure

    Time frame: Month 11

    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).

  2. Incidence of the Need for a Change in the Immunosuppressive Regimen

    Time frame: Month 11

    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).

  3. Incidence of Renal Deterioration

    Time frame: Baseline, Month 11

    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.

  4. Renal Function (cGFR)

    Time frame: Month 5

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

  5. Incidence of Treated BPAR

    Time frame: Month 11

    The incidence of treated BPAR was estimated using crude rate estimation (relative frequency).

  6. Patient and Graft Survival

    Time frame: Month 11

    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.

  7. Hepatitis C Virus (HCV) Replication in HCV-positive Patients

    Time frame: Baseline, Month 5

    HCV ribonucleic acid (RNA) was measured by real time reverse transcriptase polymerase chain reaction (PCR; copies per mL).

  8. Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death

    Time frame: From randomization to Month 11

    Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.

  9. Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Death

    Time frame: Month 12 to Month 59 post-baseline

    Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2006
Primary completion
2013
Study completion
2013
First posted
Sep 19, 2006
Registry last updated
Feb 6, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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