Progression of Renal Interstitial Fibrosis / Tubular Atrophy (IF/TA) According to Epithelial-mesenchymal Transition (EMT) and Immunosuppressive Regimen (Everolimus Based Versus CNI Based) in de Novo Renal Transplant Recipients - Full Text View

Purpose

Recently, early biomarkers of renal interstitial fibrosis have been identified, amongst them de novo expression of vimentin by tubular epithelial cells, which is an intermediate filament, and the translocation of beta-catenin into their cytoplasm. These markers, when present, suggest that the epithelial cell undergoes a phenomenon well known as "epithelial to mesenchymal transition" (EMT) and could behaves like a myo-fibroblast. EMT is highly instrumental in several models of tissue fibrosis, including in the kidney. Actually, it has not only been demonstrated that these markers are detectable in the renal graft at an early time point post-transplant (i.e. as soon as three months), but also that the intensity of their expression correlates with the progression of interstitial fibrosis of the graft between 3 and 12 months

Condition	Intervention	Phase
Renal Interstitial Fibrosis	Drug: Everolimus + enteric-coated mycophenolate sodium + Steroids Drug: Cyclosporine A+EC-MPA+steroids	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:	Prospective, Multicenter, Randomized Open Study to Evaluate the Progression of Renal Graft Fibrosis According to the Epithelial-mesenchymal Transition (EMT) in de Novo Renal Transplant Recipients Treated Either by a CNI Free Immunosuppressive Regimen With Everolimus and Enteric-coated Mycophenolate Sodium or a CNI Based Regimen With Cyclosporine and Enteric-coated Mycophenolate Sodium

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

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

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Progression of IF/TA (increase ≥ 1 in IF/TA grade according to Banff 200-2007) between M3 and M12 according to EMT profile and to treatment [ Time Frame: M3 and M12 post transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence and severity of IF/TA [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]

Enrollment:	193
Study Start Date:	September 2009
Study Completion Date:	June 2012
Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: CsA+EC-MPA Cyclosporine + enteric-coated mycophenolate sodium + Steroids	Drug: Cyclosporine A+EC-MPA+steroids C0-monitored Cyclosporine A levels 1.44 mg enteric coated mycophenolate sodium (EC-MPA) Other Name: Neoral+Myfortic
Experimental: Everolimus+EC-MPA Everolimus + enteric-coated mycophenolate sodium + Steroids	Drug: Everolimus + enteric-coated mycophenolate sodium + Steroids 1.5 mg b.i.d. Other Name: Certican + Myfortic

Eligibility

Ages Eligible for Study:	19 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Main inclusion criteria at time of transplantation:

Primary or secondary deceased or living (related or not) donor kidney transplant
Cold ischemia time < 30 hours
Main exclusion criteria at time of transplantation
PRA ≥20%
Multi-organ transplantation including dual kidneys or previous transplant with any other organ different from kidney
Non-heart beating donor
ABO incompatibility or T positive cross match
Main inclusion criteria at time of randomization
Adequate renal biopsy at M3
Main exclusion criteria at time of randomization
Histological proven acute rejection before randomization (including sub clinical acute rejection on M3 renal biopsy)
Calculated GFR < 30 ml/min
Proteinuria ≥ 1g/24h
Uncontrolled hypercholesterolemia ≥ 901 mmol/l(≥350 mg/dl) or hypertriglyceridemia ≥8.5 mmol/l (≥750mg/dl)
Thrombocytopenia (≤75 000/m3), absolute neutrophils count ≤1 500/m3 leukocytopenia ≤2 500/m3 and /or hemoglobin < 8g/dl
ASAT / ALAT total bilirubin ≥ 3UNL
Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01079143

Locations

France
Novartis Investigative Site
Caen, Cedex, France, 14033
Novartis Investigative Site
Amiens cedex1, France, 80054
Novartis Investigative Site
Angers, France, 49 033
Novartis Investigative Site
Bordeaux Cedex, France, 33076
Novartis Investigative Site
Brest, France, 29200
Novartis Investigative Site
Creteil, France, 94010
Novartis Investigative Site
Grenoble, France, 38043
Novartis Investigative Site
Le Kremlin Bicetre, France, 94275
Novartis Investigative Site
Lille Cedex, France, 59037
Novartis Investigative Site
Lyon, France, 69 437
Novartis Investigative Site
Nice Cedex 1, France, 06602
Novartis Investigative Site
Paris, France, 75475
Novartis Investigative Site
Paris, France, 75970
Novartis Investigative Site
Paris cedex 15, France, 75015
Novartis Investigative Site
Pierre Benite Cedex, France, 69495
Novartis Investigative Site
Poitiers, France, 86000
Novartis Investigative Site
Reims, France, 51092
Novartis Investigative Site
St Priest en Jarez Cedex, France, 42277
Novartis Investigative Site
Strasbourg, France, 67091
Novartis Investigative Site
Suresnes, France, 92150
Novartis Investigative Site
Toulouse Cedex 4, France, 31054
Novartis Investigative Site
Tours Cedex, France, 37044
Novartis Investigative Site
Vandoeuvre Les Nancys, France, 54511

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01079143 History of Changes
Other Study ID Numbers:	CRAD001AFR10, 2009-011473-33
Study First Received:	March 1, 2010
Last Updated:	June 4, 2013
Health Authority:	United States: Food and Drug Administration France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Novartis:

De Novo renal transplantation

Additional relevant MeSH terms:

Fibrosis
Lung Diseases, Interstitial
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Cyclosporins
Cyclosporine
Mycophenolic Acid
Immunosuppressive Agents
Mycophenolate mofetil
Everolimus
Sirolimus
Enzyme Inhibitors

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on June 17, 2013

Progression of Renal Interstitial Fibrosis / Tubular Atrophy (IF/TA) According to Epithelial-mesenchymal Transition (EMT) and Immunosuppressive Regimen (Everolimus Based Versus CNI Based) in de Novo Renal Transplant Recipients (CERTITEM)