A National Multi-center Randomized, Open Label Study to Evaluate Efficacy and Safety of Everolimus With EC-MPS Compared to Standard Treatment Combination Tacrolimus and EC-MPS in de Novo Liver Transplant Recipients (SIMCER)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01625377
First received: June 19, 2012
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

The aims of the study are to evaluate the safety and efficacy of early introduction one month post-transplantation of everolimus associated to EC-MPS with tacrolimus discontinuation in de novo liver transplant recipients and to evaluate if it leads to a better renal function 6 month post-transplantation compared to standard treatment associating tacrolimus and EC-MPS.

The renal function is estimated by glomerular filtration rate.


Condition Intervention Phase
Liver Transplantation
Drug: tacrolimus
Drug: everolimus
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: Etude Nationale Multicentrique, randomisée, en Ouvert, évaluant l'efficacité et la tolérance de l'évérolimus associé au mycophénolate Sodique, en Comparaison à un Traitement Standard Associant Tacrolimus et mycophénolate Sodique Chez Des Patients Adultes transplantés hépatiques de Novo

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change from baseline in renal function [ Time Frame: randomisation to month 6 post-transplantation ] [ Designated as safety issue: No ]
    Change in glomerular filtration rate calculated using the MDRD abbreviated formula


Secondary Outcome Measures:
  • Treatment failures (biopsy proven acute rejection BPAR, graft loss or death) [ Time Frame: randomization to 6 months after transplantation ] [ Designated as safety issue: No ]
    Incidence of treated biopsy proven acute rejection BPAR (score > 3), graft loss or death

  • BPAR [ Time Frame: 3 months and 6 months after transplantation ] [ Designated as safety issue: No ]
    Incidence of BPAR

  • Treated BPAR [ Time Frame: 3 months and 6 months after transplantation ] [ Designated as safety issue: No ]
    Incidence of treated BPAR

  • Treated BPAR (score > 3) [ Time Frame: 3 months and 6 months after transplantation ] [ Designated as safety issue: No ]
    Incidence of treated BPAR (score > 3)

  • BPAR (score > 3) [ Time Frame: 3 months and 6 months after transplantation ] [ Designated as safety issue: No ]
    Incidence of BPAR (score > 3)

  • Death or graft loss [ Time Frame: 6 months after transplantation ] [ Designated as safety issue: No ]
    Incidence of death or graft loss

  • Change from baseline in renal function [ Time Frame: 3 months and 6 months after transplantation ] [ Designated as safety issue: No ]
    change in renal function parameters (creatininemia, eGFR, estimated creatinine clearance, proteinuria, microalbuminuria and proteninuria/microalbuminuria ratio)

  • Assessment of safety [ Time Frame: 3 months and 6 months post-transplantation ] [ Designated as safety issue: Yes ]
    Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs). Incidence of premature study and study treatment discontinuations and discontinuation reasons.


Estimated Enrollment: 205
Study Start Date: December 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Control group (Arm 1)
From transplantation to randomization: Simulect® (40mg) at D0 and D4 + Prograf® (C0 6-10 ng/ml) from D3-D5 + Myfortic® 1440 mg/d ± steroids From randomization to month 6 : Prograf® (C0 6-10 ng/ml) + Myfortic® 1440 mg/d ± steroids
Drug: tacrolimus
Arm 1 : tacrolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to 16 weeks post-transplantation at the latest.
Other Name: Prograf®
Experimental: Everolimus (Arm 2)
From transplantation to randomization: Simulect® (40mg) at D0 and D4 + Prograf® (C0 6-10 ng/ml) from D3-D5 + Myfortic® 1440 mg/d ± steroids From randomization to month 6 : Certican® (C0 6-10 ng/ml) + Myfortic® 1440 mg/d ± steroids
Drug: tacrolimus
Arm 1 : tacrolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from D3-D5 post-transplantation to 16 weeks post-transplantation at the latest.
Other Name: Prograf®
Drug: everolimus
Arm 1: no everolimus Arm 2: everolimus (C0 6-10 ng/ml) from randomization to month 6 post-transplantation
Other Name: Certican® / RAD001

  Eligibility

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

Inclusion Criteria:

  • Man or woman aged 18 years or greater, recipient of a primary liver transplant from a deceased donor with whole or split liver

Exclusion Criteria:

  • Patient recipient of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant
  • Recipient of a liver from a living donor or cadaveric non heart beating donor
  • ABO incompatible transplant graft
  • Transplantation following autoimmune liver hepatitis, primitive sclerosing cholangitis or primitive biliary cirrhosis
  • Estimated glomerular filtration rate ≤ 30ml/min at selection
  • History of malignancy within the 5 past years, other than non-metastatic basal or squamous cell carcinoma and hepatocellular carcinoma
  • Alpha-foeto-protein > 1000 ng/ml (only in case of hepatocellular carcinoma) 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: NCT01625377

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
France
Novartis Investigative Site Recruiting
Besancon cedex, France, 25030
Novartis Investigative Site Recruiting
Bordeaux Cedex, France, 33076
Novartis Investigative Site Recruiting
Chambrey les Tours, France, 37044
Novartis Investigative Site Recruiting
Clichy, France, 92110
Novartis Investigative Site Recruiting
Creteil, France, 94010
Novartis Investigative Site Recruiting
Grenoble, France, 38043
Novartis Investigative Site Recruiting
Lille Cedex, France, 59037
Novartis Investigative Site Not yet recruiting
Lyon, France, 69437
Novartis Investigative Site Recruiting
Marseille, France, 13385
Novartis Investigative Site Recruiting
Montpellier, France, 34295
Novartis Investigative Site Recruiting
Nice, France, 06202
Novartis Investigative Site Recruiting
Paris, France, 75012
Novartis Investigative Site Recruiting
Paris Cedex 13, France, 75651
Novartis Investigative Site Recruiting
Rennes Cedex, France, 35033
Novartis Investigative Site Recruiting
Toulouse Cedex 4, France, 31054
Novartis Investigative Site Recruiting
Villejuif, France, 94800
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: NCT01625377     History of Changes
Other Study ID Numbers: CRAD001HFR02, 2012-000137-39
Study First Received: June 19, 2012
Last Updated: June 18, 2014
Health Authority: France: L'Agence nationale de sécurité du médicament et des produits de santé (ANSM)

Keywords provided by Novartis:
Everolimus, liver transplantation, early introduction, renal function

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 July 28, 2014