Efficacy, Safety and Evolution of Cardiovascular Parameters in Renal Transplant Recipients

NCT01114529 | Completed Phase 3 Results DMC

• 2 other identifiers: CRAD001A24292009-015918-22
• Study Type: interventional
• Target: 828
• Locations: 19 countries
• Sites: 66

Brief Summary

The purpose of this study was to determine whether an early Calcineurin Inhibitor (CNI) to everolimus conversion at 10-14 weeks post transplantation improves renal allograft function without compromising efficacy compared to standard CNI treatment in de novo renal allograft recipients. In addition, the study was designed to evaluate the impact of a CNI-free regimen on evolution of cardiovascular parameters in de novo renal allograft recipients

Conditions

Kidney Transplantation

Keywords

de novo renal allograft recipients; renal allograft function; CNI-free regimen

Outcome Measures

Primary Outcomes (1)

• Estimated Glomerular Filtration Rate (eGFR)

  Assessment of renal function by comparing change from randomization to Month 12 in eGFR (MDRD4) between treatment arms (Full analysis set). Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR \[mL/min/1.73m˄2\] = 186.3\*(C˄-1.154)\*(A˄-0.203)\*G\*R. DEFINITIONS: C = serum concentration of creatinine \[mg/dL\]; A = age \[years\]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1

  Month 12

Secondary Outcomes (3)

• Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24

  at 12 months and month 24 post-transplantation

• Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24

  Randomization, Month 12 and Month 24

• Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis)

  at 24 months post-transplantation

Study Arms (2)

Everolimus

EXPERIMENTAL

Conversion from CNI to everolimus in combination with Myfortic and steroids

Drug: Everolimus

Calcineurin inhibitor, Prograf or Neoral

ACTIVE COMPARATOR

Control arm: CNI continuation, either Prograf or Neoral in combination with Myfortic and steroids

Drug: Prograf or Neoral

Interventions

Everolimus DRUG

Early CNI to everolimus conversion

Also known as: Certican, Zortress, RAD001

Everolimus

Prograf or Neoral DRUG

Active CNI-based control (Prograf or Neoral)

Also known as: Tacrolimus or Cyclosporine

Calcineurin inhibitor, Prograf or Neoral

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female renal allograft recipients at least 18 years old.
• Written informed consent.
• Patient receiving a primary or secondary kidney transplant from a cadaveric or living unrelated-/related donor.
• Cold ischemia time (CIT) \< 24 hours.
• Negative pregnancy test for female patients.
• Patients on CNI (TAC or CsA) + Myfortic + steroids.
• Serum creatinine \< 2.8 mg/dL (250 µmol/L) and an actual eGFR (MDRD4) ≥ 25 mL/min/1.73m exp2 (without renal replacement therapy).

You may not qualify if:

• Recipient of multiple organ transplants.
• Recipient of ABO incompatible allograft or a positive cross-match.
• Panel Reactive Antibodies (PRA) level ≥ 30 %.
• Positive test for human immunodeficiency virus (HIV).
• Patient receiving an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor.
• HBsAg and/or a HCV positive patient with evidence of elevated LFTs (ALT/AST levels ≥ 2.5 times ULN).
• Severe restrictive or obstructive pulmonary disorders.
• Patient with severe allergy requiring acute or chronic treatment or hypersensitivity to any of the study drugs or similar drugs.
• Severe hypercholesterolemia or hypertriglyceridemia.
• Low platelet count.
• Low white blood cell count.
• History of malignancy of any organ system
• Graft loss.
• Patient on renal replacement therapy.
• Patient who experienced severe humoral and/or cellular rejection (BANFF ≥ IIb).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (77)

Novartis Investigative Site

CABA, Buenos Aires, C1118AAT, Argentina

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San Martín, Buenos Aires, C1107BEA, Argentina

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Resistencia, Chaco Province, H3508AZP, Argentina

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Córdoba, X5016JDA, Argentina

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Córdoba, X5016KEH, Argentina

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Córdoba, X5022CPU, Argentina

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Santa Fe, S3000EPV, Argentina

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Camperdown, New South Wales, 2050, Australia

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Adelaide, South Australia, 5000, Australia

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Clayton, Victoria, 3168, Australia

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Melbourne, Victoria, 3050, Australia

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Linz, A-4010, Austria

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Linz, A-4020, Austria

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Vienna, 1090, Austria

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Leuven, 3000, Belgium

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Tartu, 51014, Estonia

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Brest, 29200, France

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Nice, 06602, France

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Toulouse, 31054, France

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Tours, 37044, France

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Vandœuvre-lès-Nancy, 54511, France

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Aachen, 52074, Germany

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Berlin, 12203, Germany

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Essen, 45147, Germany

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Frankfurt am Main, 60596, Germany

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Hamburg, 20246, Germany

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Hannover Muenden, 34346, Germany

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Heidelberg, 69120, Germany

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Münster, 48149, Germany

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Pátrai, Greece, 265 00, Greece

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Athens, GR 11527, Greece

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Athens, GR-106 76, Greece

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Visakhapatnam, Andhra Pradesh, India

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Bangalore, Karnataka, 560 055, India

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New Delhi, National Capital Territory of Delhi, 110017, India

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Lucknow, Uttar Pradesh, 226014, India

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New Delhi, 110044, India

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Bologna, BO, 40138, Italy

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Padua, PD, 35128, Italy

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Roma, RM, 00144, Italy

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Siena, SI, 53100, Italy

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Torino, TO, 10126, Italy

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Riga, 1002, Latvia

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Vilnius, LT-08661, Lithuania

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Torreón, Coahuila, 27250, Mexico

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Mexico City, Mexico City, 14080, Mexico

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Aguascalientes, 20230, Mexico

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Veracruz, 91700, Mexico

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Amsterdam, 1105 AZ, Netherlands

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Groningen, 9713 GZ, Netherlands

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Leiden, 2300 RC, Netherlands

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Oslo, 0424, Norway

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Carnaxide - Linda-A-Velha, Lisbon District, 2790-134, Portugal

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Lisbon, 1069-166, Portugal

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Porto, 4200-319, Portugal

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Cluj-Napoca, Jud Cluj, 400006, Romania

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Krasnodar, 350086, Russia

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Moscow, 115446, Russia

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Moscow, 123182, Russia

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Nizhny Novgorod, 603000, Russia

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Novosibirsk, 630087, Russia

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S.-Petersburg, 192242, Russia

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Samara, 443079, Russia

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Volzhskiy, 404120, Russia

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Málaga, Andalusia, 29010, Spain

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Santander, Cantabria, 39008, Spain

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Barcelona, Catalonia, 08003, Spain

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Barcelona, Catalonia, 08036, Spain

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L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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A Coruña, Galicia, 15006, Spain

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Zaragoza, 50009, Spain

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Khon Kaen, THA, 40002, Thailand

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Bangkok, 10330, Thailand

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Antalya, 07000, Turkey (Türkiye)

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Büyükçekmece / Ýstanbul, 34520, Turkey (Türkiye)

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Fatih / Istanbul, 34098, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

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Related Links

• The American Journal of Transplantation, Poster Abstracts, 2016 Provider: John Wiley \& Sons, Ltd

MeSH Terms

Interventions

Everolimus; Tacrolimus; Cyclosporine

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

+1(862)778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2010
• First Posted: May 3, 2010
• Study Start: August 9, 2010
• Primary Completion: October 30, 2014
• Study Completion: October 30, 2014
• Last Updated: May 30, 2017
• Results First Posted: May 30, 2017

Record last verified: 2017-04

Locations

IT (5); AU (3); RU (8); RO (1); ES (1); GR (3); NL (3); TU (4); TH (2); NO (1); PT (3); FR (5); DE (8); IN (5); LI (1); BE (1); AR (7); LA (1); ME (4)