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

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:

MedlinePlus related topics: Liver Transplantation

Drug Information available for: Mycophenolic acid Mycophenolate sodium Sirolimus Tacrolimus Mycophenolate mofetil hydrochloride Mycophenolate mofetil Everolimus Temsirolimus

U.S. FDA Resources

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
Incidence of biopsy proven acute rejection (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 biopsy proven acute rejection (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:	184
Study Start Date:	June 2012
Estimated Primary Completion Date:	December 2014 (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 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 D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from 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 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 D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from 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

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 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 D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from 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 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 D5 post-transplantation to month 6 post-transplantation. Arm 2 : tacolimus (C0 6-10 ng/ml) from 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 Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01625377

Contacts

Contact: Novartis Pharmaceuticals

+41 61 324 1111

Locations

France
Novartis Investigative Site	Not yet recruiting
Besancon cedex, France, 25030
Novartis Investigative Site	Not yet recruiting
Bordeaux Cedex, France, 33076
Novartis Investigative Site	Not yet recruiting
Chambrey les Tours, France, 37044
Novartis Investigative Site	Not yet recruiting
Clichy, France, 92110
Novartis Investigative Site	Not yet recruiting
Creteil, France, 94010
Novartis Investigative Site	Not yet recruiting
Grenoble, France, 38043
Novartis Investigative Site	Not yet recruiting
Lille Cedex, France, 59037
Novartis Investigative Site	Not yet recruiting
Lyon, France, 69437
Novartis Investigative Site	Not yet recruiting
Marseille, France, 13385
Novartis Investigative Site	Not yet recruiting
Montpellier, France, 34295
Novartis Investigative Site	Not yet recruiting
Nice, France, 06202
Novartis Investigative Site	Not yet recruiting
Paris, France, 75012
Novartis Investigative Site	Not yet recruiting
Paris Cedex 13, France, 75651
Novartis Investigative Site	Not yet recruiting
Rennes Cedex, France, 35033
Novartis Investigative Site	Not yet recruiting
Toulouse Cedex 4, France, 31054
Novartis Investigative Site	Not yet recruiting
Villejuif, France, 94800

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

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 20, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Novartis:

Everolimus, liver transplantation, early introduction, renal function

Additional relevant MeSH terms:

Mycophenolic Acid
Sirolimus
Mycophenolate mofetil
Everolimus
Tacrolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 21, 2013

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