Trial record 10 of 59 for:    "Living Donors" | Open Studies

Efficacy and Safety of Everolimus in Liver Transplant Recipients of Living Donor Liver Transplants

This study is currently recruiting participants.
Verified February 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01888432
First received: June 15, 2013
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

The purpose of this trial is to demonstrate the efficacy and safety of everolimus in combination with reduced tacrolimus, compared to tacrolimus control, in living donor liver transplant recipients.


Condition Intervention Phase
Liver Transplantation
Drug: Everolimus + reduced tacrolimus
Drug: Standard tacrolimus
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 24 Month, Randomized, Controlled, Study to Evaluate the Efficacy and Safety of Concentration-controlled Everolimus Plus Reduced Tacrolimus Compared to Standard Tacrolimus in Recipients of Living Donor Liver Transplants

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Composite efficacy failure of treated biopsy proven acute rejection, graft loss or death in everolimus with reduced tacrolimus group compared to standard tacrolimus [ Time Frame: at 12 months post transplantation ] [ Designated as safety issue: No ]
    Rate of composite efficacy failure of treated biopsy proven acute rejection (tBPAR ≥ RAI score 3), graft loss (GL) or death (D) in everolimus with reduced tacrolimus group compared to standard tacrolimus at 12 months


Secondary Outcome Measures:
  • Renal function by estimated Glomerular Filtration Rate [ Time Frame: Randomization, Month 12 ] [ Designated as safety issue: No ]
    Renal function (change in estimated glomerular filtration rate (eGFR)) from randomization to Month 12 post transplantation with everolimus (EVR) in combination with reduced tacrolimus (rTAC) compared to standard exposure tacrolimus (TAC) in living donor liver transplant recipients

  • Compare incidence of a composite of tBPAR, graft loss, death. Incidenceof each component of the composite. Incidenceof a composite of death or graft loss. Incidence of BPAR, tAR and AR. [ Time Frame: Month 12 and Month 24 post transplantation ] [ Designated as safety issue: No ]
    Compare between the treatment group EVR with rTAC vs standard TAC: incidence of a composite of tBPAR, graft loss, death. Incidenceof each component of the composite. Incidenceof a composite of death or graft loss. Incidence of BPAR, tAR and AR.

  • Compare tBPAR and tAR by severity (RAI grading) as well as diagnosis leading to transplantation [ Time Frame: Month 6, Month 12 and Month 24 ] [ Designated as safety issue: No ]
    Compare tBPAR and tAR by severity (RAI grading) as well as diagnosis leading to transplantation

  • Incidence of treated BPAR by time to event, severity, and diagnosis leading to transplantation [ Time Frame: Month 12 and Month 24 ] [ Designated as safety issue: No ]
    Incidence of treated BPAR by time to event, severity, and diagnosis leading to transplantation

  • Compare evolution of post-randomization renal function over time assessed by the change by eGFR [ Time Frame: Randomization, Month 12 and Month 24 ] [ Designated as safety issue: No ]
    Compare evolution of post-randomization renal function over time assessed by the change in estimated GFR (MDRD-4), including changes from randomization to Months 12 and 24. Rate of change of renal function.

  • Renal function and change in eGFR in subgroups [ Time Frame: Randomization, Month 6 and 12 ] [ Designated as safety issue: No ]
    Renal function and change in estimated GFR in subgroups including age (< 60 and ≥ 60 years), gender, race, region, renal function strata, HCV status, MELD score categories, and diagnosis leading to transplantation

  • Urinary protein/creatinine ratio at various time points [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
    Urinary protein/creatinine ratio at various time points

  • Compare rate of recurrence and time to recurrence of HCC in subjects with a diagnosis of HCC at the time of liver transplantation [ Time Frame: Randomization, Month12 and Month 24 ] [ Designated as safety issue: No ]
    Compare rate of recurrence and time to recurrence of HCC in subjects with a diagnosis of HCC at the time of liver transplantation

  • Compare tumor-free survival in subjects with a diagnosis of HCC at the time of liver transplantation [ Time Frame: Randomization, Month 24 ] [ Designated as safety issue: No ]
    Compare tumor-free survival in subjects with a diagnosis of HCC at the time of liver transplantation

  • Compare HCV viral load (overall and by genotype). [ Time Frame: Month 12 and 24 ] [ Designated as safety issue: No ]
    Compare HCV viral load (overall and by genotype).

  • Compare rate of progression of HCV related allograft fibrosis. [ Time Frame: Randomization, Month 24 ] [ Designated as safety issue: No ]
    Compare rate of progression of HCV related allograft fibrosis.

  • Compare incidence of AEs and SAEs including infections and serious infections, overall, by body system and preferred term [ Time Frame: Month 24 ] [ Designated as safety issue: Yes ]
    Compare incidence of AEs and SAEs including infections and serious infections, overall, by body system and preferred term


Estimated Enrollment: 470
Study Start Date: September 2013
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + reduced tacrolimus
Everolimus + reduced tacrolimus ± corticosteroids
Drug: Everolimus + reduced tacrolimus
Everolimus will be initiated at Week 4 post transplantation. The dose will be adjusted to maintain the everolimus trough blood levels between 3-8 ng/mL for the duration of the study. Tacrolimus will be reduced to 3-5 ng/mL.
Active Comparator: Standard tacrolimus
Standard tacrolimus ± corticosteroids
Drug: Standard tacrolimus
Tacrolimus will be initiated as soon as possible after transplantation according to approved labeling recommendations. The trough level should be 5-15 ng/mL until randomization, 8-12 ng/mL from randomization until month 4 and after month 4 until end of study reduced to 6 -10 ng/mL.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Written informed consent
  • Subject aged ≥18 years of a primary, orthotopic liver allograft, from a living donor
  • Subject negative for HIV

Incusion criteria at Randomization:

- Subject was initated on tacrolimus-based immunosuppressive regimen with steroids and other immunosuppression

Exclusion criteria:

  • Subjects transplanted for acute liver failure
  • HCV negativesubjects receiving a transplant from HCV positive donor
  • Subjects receiving multiple solid organ (including multiple liver lobes/segments) or islet cell tissue transplants, or have previously received an organ or tissue transplant.
  • Subjects receiving an ABO incompatible allograft.
  • MELD-score > 35 within 1 month prior to transplantation.
  • Use of immunosuppressive or antibody induction agents not specified in the protocol.
  • History of malignancy of any organ system (except hepatocellular carcinoma or localized basal cell carcinoma of the skin)
  • Hepatocellular carcinoma with extrahepatic spread or macrovascular invasion
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 2 weeks of the last dose of study medication
  • History of hypersensitivity to any of the study drugs or to drugs with similar chemical class, or to any of the excipients

Exclusion criteria at Randomization:

  • Any post-transplant history of thrombosis, occlusion or stent placement in any major hepatic artery, major/reconstructed hepatic vein, portal vein or inferior vena cava at any time during the run-in period prior to randomization.
  • Subjects with a confirmed spot urine protein/creatinine ratio that indicates ≥ 1.0 g/24 hrs of proteinuria
  • Subjects who have severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >8.5 mmol/L) at randomization.
  • Subjects with platelet count < 30,000/mm3.
  • Subjects with an absolute neutrophil count of < 1,000/mm³ or white blood cell count of < 2,000/mm³.
  • Subjects with systemic infection requiring active use of IV antibiotics.
  • Subjects requiring life support measures such as ventilation, dialysis, vasopressor agents.
  • Subjects who require renal replacement therapy within 7 days prior to randomization.
  • Subjects with detectable HBV DNA at time of randomization
  • Subjects meeting the following criteria for acute rejection during the run in period:

    • Any acute rejection in the week prior to randomization.
    • 2 treated acute rejections.
    • Any rejection requiring antibody treatment.
    • Any severe cellular (and/or any humoral) rejection. Other protocol-defined inclusion/exclusion criteria may apply.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01888432

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 42 Study Locations
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: NCT01888432     History of Changes
Other Study ID Numbers: CRAD001H2307, 2010-024527-25
Study First Received: June 15, 2013
Last Updated: February 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
liver transplantation
everolimus
tacrolimus
reduced calcineuron inhibitor
renal function
living donor

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

ClinicalTrials.gov processed this record on April 15, 2014