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

Liver Transplantation Clinical Trial

— SIMCER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01625377
• Other study ID #: CRAD001HFR02
• Secondary ID: 2012-000137-39
• Status: Completed
• Phase: Phase 3
• First received: June 19, 2012
• Last updated: November 30, 2015
• Start date: December 2012
• Est. completion date: March 2015

Study information

• Verified date: November 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: L'Agence nationale de sécurité du médicament et des produits de santé (ANSM)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 191
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

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.
• everolimus
Arm 1: no everolimus Arm 2: everolimus (C0 6-10 ng/ml) from randomization to month 6 post-transplantation

Locations

Country	Name	City	State
France	Novartis Investigative Site	Besancon cedex
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Chambray les Tours
France	Novartis Investigative Site	Clichy
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris Cedex 13
France	Novartis Investigative Site	Rennes Cedex
France	Novartis Investigative Site	Toulouse Cedex 4
France	Novartis Investigative Site	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in renal function	Change in glomerular filtration rate calculated using the MDRD abbreviated formula	randomisation to month 6 post-transplantation	No
Secondary	Treatment failures (biopsy proven acute rejection BPAR, graft loss or death)	Incidence of treated biopsy proven acute rejection BPAR (score > 3), graft loss or death	randomization to 6 months after transplantation	No
Secondary	BPAR	Incidence of BPAR	3 months and 6 months after transplantation	No
Secondary	Treated BPAR	Incidence of treated BPAR	3 months and 6 months after transplantation	No
Secondary	Treated BPAR (score > 3)	Incidence of treated BPAR (score > 3)	3 months and 6 months after transplantation	No
Secondary	BPAR (score > 3)	Incidence of BPAR (score > 3)	3 months and 6 months after transplantation	No
Secondary	Death or graft loss	Incidence of death or graft loss	6 months after transplantation	No
Secondary	Change from baseline in renal function	change in renal function parameters (creatininemia, eGFR, estimated creatinine clearance, proteinuria, microalbuminuria and proteninuria/microalbuminuria ratio)	3 months and 6 months after transplantation	No
Secondary	Assessment of safety	Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs). Incidence of premature study and study treatment discontinuations and discontinuation reasons.	3 months and 6 months post-transplantation	Yes