Efficacy, Tolerability and Safety of Early Introduction of Everolimus, Reduced Calcineurin Inhibitors and Early Steroid Elimination Compared to Standard CNI, Mycophenolate Mofetil and Steroid Regimen in Paediatric Renal Transplant Recipients

NCT ID: NCT01544491

Last Updated: 2019-05-31

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

106 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-17

Study Completion Date

2018-09-24

Brief Summary

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The purpose of this study is to determine if everolimus combined with reduced exposure CNI (TAC) is efficacious and safe and will support corticosteroid elimination compared to a standard exposure CNI (TAC) + MMF + steroid regimen after paediatric kidney transplantation. An additional purpose of the study is to assess the effect of the combination of EVR and reduced exposure CNI (TAC) on renal function.

This study is part of the requirements of the Paediatric Investigational Plan approved by Paediatric Committee at the European Medicines Agency (PDCO/EMA) on September 10, 2010, and is intended to support the indication of everolimus in the prevention of acute rejection in paediatric recipients of a renal transplant.

Detailed Description

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Conditions

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Prevention of Acute Rejection in Paediatric Recipients of a Renal Transplant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Investigational arm

Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant

Group Type EXPERIMENTAL

RAD001

Intervention Type DRUG

Everolimus (C0 trough level of 3-8 ng/mL) in combination with reduced dose tacrolimus and steroids withdrawal at 6 months after transplant

Control arm

MMF continuation (in combination with tacrolimus and standard dose steroids)

Group Type ACTIVE_COMPARATOR

MMF

Intervention Type DRUG

MMF (Cellcept®): 600mg/m2/dose twice daily (1200 mg/m2/day) in combination with tacrolimus (Prograf) and standard dose steroids

Interventions

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RAD001

Everolimus (C0 trough level of 3-8 ng/mL) in combination with reduced dose tacrolimus and steroids withdrawal at 6 months after transplant

Intervention Type DRUG

MMF

MMF (Cellcept®): 600mg/m2/dose twice daily (1200 mg/m2/day) in combination with tacrolimus (Prograf) and standard dose steroids

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Written informed consent/assent must be obtained from the parent(s) or legal guardian before any assessment is performed.
2. Primary or secondary paediatric kidney transplant recipient aged greater than or equal to 1 year and younger than 18 years receiving a deceased donor or non-HLA identical living donor (related or unrelated) renal transplant.


1. Patients on TAC + MMF + steroids.
2. Renal function with eGFR \> 40 ml/min/1.73 m2 (Schwartz formula - abbreviated).

Exclusion Criteria

1. Recipients of kidneys from donors with known renal disease (such as diabetes nephropathy, nephrosclerosis), at the time of transplant.
2. Recipients of a kidney with a cold ischemia time \> 24 hours.
3. History of hypersensitivity or contraindications to any of the study drugs or to drugs of similar chemical classes, or to any of the excipients.
4. History of malignancy of any organ system treated or untreated, carrying possible risk of recurrence according to current guidelines (Appendix 10 of protocol).


1. Use of other investigational drugs at the time of randomization, or within 30 days or 5 half-lives prior randomization, whichever is longer.
2. Patients with ongoing or recently (within 2 weeks prior to randomization) treated episodes of acute rejection (any grade) or a steroid resistant acute rejection at the time of randomization.
3. Patients who experienced acute cellular rejection (Banff ≥1B) or any antibody mediated acute rejection or patients considered at high risk of antibody mediated acute rejection by the investigator assessment (e.g. presence of newly formed DSA, histological suspicion) at any time before randomization (as the DSA quantitative threshold to define high risk is not fully established, the assessment of the risk will be made after discussion between the laboratory expert and the investigator who will take into account all information available and apply best judgment).
4. Patients with ongoing wound healing problems, clinically significant wound infection requiring continued therapy or other severe surgical complication in the opinion of the investigator.
5. Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) and can not discontinue the treatment (see Appendix 6 for list of medications).
6. Patients with nephrotic range proteinuria (protein to creatinine ratio ≥2.0 mg/mg or 200 mg/mmol (Hogg, 2003).
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Los Angeles, California, United States

Site Status

Novartis Investigative Site

Ann Arbor, Michigan, United States

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Novartis Investigative Site

St Louis, Missouri, United States

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Novartis Investigative Site

Santa Fe, , Argentina

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Porto Alegre, Rio Grande do Sul, Brazil

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São Paulo, São Paulo, Brazil

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Bron, , France

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Lille, , France

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Paris, , France

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Paris, , France

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Berlin, , Germany

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Essen, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Münster, , Germany

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Tübingen, , Germany

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Budapest, , Hungary

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Bologna, BO, Italy

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Genova, GE, Italy

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Roma, ITA, Italy

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Padua, PD, Italy

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Torino, TO, Italy

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Oslo, , Norway

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Warsaw, , Poland

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Esplugues de Llobregat, Barcelona, Spain

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Stockholm, , Sweden

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Novartis Investigative Site

Antalya, , Turkey (Türkiye)

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Novartis Investigative Site

London, , United Kingdom

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Novartis Investigative Site

Manchester, , United Kingdom

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Novartis Investigative Site

Nottingham, , United Kingdom

Site Status

Countries

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United States Argentina Brazil France Germany Hungary Italy Norway Poland Spain Sweden Turkey (Türkiye) United Kingdom

References

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Patry C, Sauer LD, Sander A, Krupka K, Fichtner A, Brezinski J, Geissbuhler Y, Aubrun E, Grinienko A, Strologo LD, Haffner D, Oh J, Grenda R, Pape L, Topaloglu R, Weber LT, Bouts A, Kim JJ, Prytula A, Konig J, Shenoy M, Hocker B, Tonshoff B. Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry. Pediatr Nephrol. 2023 May;38(5):1621-1632. doi: 10.1007/s00467-022-05777-x. Epub 2022 Oct 20.

Reference Type DERIVED
PMID: 36264431 (View on PubMed)

Tonshoff B, Tedesco-Silva H, Ettenger R, Christian M, Bjerre A, Dello Strologo L, Marks SD, Pape L, Veldandi U, Lopez P, Cousin M, Pandey P, Meier M. Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal. Am J Transplant. 2021 Jan;21(1):123-137. doi: 10.1111/ajt.16005. Epub 2020 Jun 27.

Reference Type DERIVED
PMID: 32406111 (View on PubMed)

Other Identifiers

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2010-024381-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001A2314

Identifier Type: -

Identifier Source: org_study_id

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