A Study Looking at Diabetes in Kidney Transplant Recipients Receiving Immunosuppressive Regimen With or Without Steroids (ADVANCE)

Investigating New Onset Diabetes Mellitus in Kidney Transplant Recipients Receiving an Advagraf-Based Immunosuppressive Regimen With or Without Corticosteroids - A Multicenter, Two Arm, Randomized, Open Label Clinical Study

The purpose of this study is to focus on potential differences in the occurrence of new-onset Diabetes Mellitus (a glucose metabolism disorder) when two different regimens of immunosuppressive treatment are compared.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Mycophenolate Mofetil; Drug: Advagraf; Drug: Simulect; Drug: Corticosteroids

Detailed Description

The primary objective of this study is to compare an Immunosuppressive regimen with 10 days of corticosteroids with a regimen with only an optional intra-op bolus of corticosteroids with regard to incidence of new onset Diabetes Mellitus as per the American Diabetic Association (ADA) criteria at any point up to 24 weeks after kidney transplantation.

• Study Type: Interventional
• Enrollment (Actual): 1166
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Perth, Australia, 6001
  • Sydney, Australia, 2050
  • Sydney, Australia, 2145
• Belgium
  • Brussels, Belgium, 1090
  • Bruxelles, Belgium, 1200
  • Leuven, Belgium, 3000
  • Liege, Belgium, 4000
• Colombia
  • Cali, Colombia, 760032
• Czechia
  • Brno, Czechia, 656 91
  • Hradec Kralove, Czechia, 50005
  • Olomouc, Czechia, 775 20
  • Prague, Czechia, 140 21
• Estonia
  • Tartu, Estonia, 51014
• Finland
  • Helsinki, Finland, 02611
• France
  • Bordeaux, France, 33076
  • Cite Nord, France, 42270
  • D'Angers, France, 49033
  • Le Puytren, France, 87042
  • Montpellier, France, 34295
  • Nantes, France, 49033
  • Nice, France, 06002
  • Paris, France, 75970
  • Rennes, France, 35033
  • Rouen, France, 76320
  • Strasbourg, France, 67091
  • Suresnes, France, 92151
• Germany
  • Aachen, Germany, 52074
  • Bonn, Germany, 53105
  • Düsseldorf, Germany, 40225
  • Essen, Germany, 45147
  • Halle Saale, Germany, 06120
  • Kaiserslautern, Germany, 67655
  • Mannheim, Germany, 68167
  • Muenchen, Germany, 81675
  • Regensburg, Germany, 93053
  • Rostock, Germany, 18055
• Hungary
  • Debrecen, Hungary, 4032
  • Szeged, Hungary, 6720
• Italy
  • Ancona, Italy, 60020
  • Bologna, Italy, 40138
  • Cagliari, Italy, 09134
  • L'Aquila, Italy, 67010
  • Milano, Italy, 20162
  • Milano, Italy, 20132
  • Padova, Italy, 35128
  • Pisa, Italy, 56124
  • Roma, Italy, 00133
  • Salerno, Italy, 84131
  • Treviso, Italy, 31100
  • Vicenza, Italy, 36100
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
  • Seoul, Korea, Republic of, 120-752
  • Seoul, Korea, Republic of, 135-710
  • Seoul, Korea, Republic of, 135-720
• Latvia
  • Riga, Latvia, LV-1002
• Lithuania
  • Vilnius, Lithuania, LT-08661
• Mexico
  • Cuernavaca, Mexico, 62448
  • Mexico City, Mexico, 14000
• Netherlands
  • Maastricht, Netherlands, 6229 HX
• Norway
  • Olso, Norway, 0027
• Poland
  • Bydgoszcz, Poland, 85-094
  • Gdansk, Poland, 80-952
  • Poznan, Poland, 60-479
  • Szczecin, Poland, 70-111
  • Warszawa, Poland, 02-006
• Portugal
  • Coimbra, Portugal, 3000-075
  • Lisboa, Portugal, 1649-035
  • Lisboa, Portugal, 1069-166
  • Porto, Portugal, 4099-001
• Romania
  • Bucharest, Romania, 022328
  • Lasi, Romania, 700503
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
  • Moscow, Russian Federation, 119992
  • Moscow, Russian Federation, 115446
  • Moscow, Russian Federation, 123182
  • Moscow, Russian Federation, 129110
  • Moscow, Russian Federation, 129090
  • Nizhniy Novgorod, Russian Federation, 603001
  • Omsk, Russian Federation, 644112
  • Saint-Petersburg, Russian Federation, 197022
  • Saint-Petersburg, Russian Federation, 192242
  • Vol'skiy, Russian Federation, 404120
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
  • Bratislava, Slovakia, 833 05
  • Kosice, Slovakia, 040 66
• Spain
  • Alicante, Spain, 03010
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08916
  • Cordoba, Spain, 14004
  • Madrid, Spain, 28034
  • Madrid, Spain, 28041
  • Santa Cruz de Tenerife, Spain, 38320
  • Sevilla, Spain, 41013
  • Toledo, Spain, 45004
  • Valencia, Spain, 46009
  • Valladolid, Spain, 47011
• Sweden
  • Goteborg, Sweden, 41345
  • Stockholm, Sweden, 141 86
  • Uppsala, Sweden, 75185
• Switzerland
  • Bern, Switzerland, 3010

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• End stage kidney disease and a suitable candidate for primary

kidney transplantation or re-transplantation (unless the graft was

lost from rejection within one year)

• Receiving a kidney transplant from a deceased or living (non

Human Leukocyte Antigen identical) donor with compatible AB0 blood type

• Female subjects of childbearing potential must have a

negative serum or urine pregnancy test at enrollment and must

agree to maintain highly effective birth control during the study.

A highly effective method of birth control is defined as those

which result in a low failure rate (CPMP/ICH/286/95 modified)

of less than 1% per year when used consistently and correctly

such as implants, injectables, combined oral contraceptives,

some IUDs, sexual abstinence or vasectomized partner

Exclusion Criteria:

• Receiving or having previously received an organ transplant

other than a kidney

• Cold ischemia time of the donor kidney > 30 hours
• Panel Reactive Antibody >20% (Highest level in 6 months prior to transplant)
• Previous renal transplant lost within one year for immunological reasons
• Receiving a graft from a non-heart-beating donor other than of Maastricht category 3 (withdrawal of support awaiting cardiac arrest)
• Significant liver disease, defined as having continuously

elevated SGPT/ALT and/or SGOT/AST and/or total bilirubin

levels ≥ 2 times the upper value of the normal range of the

investigational site or is receiving a graft from a hepatitis C or B

positive donor

• Diagnosis of Diabetes Mellitus prior to transplantation (treated with prescribed medications or diet controlled) or where there is evidence of a previous positive Oral Glucose Tolerance Test (OGTT) in the patients medical history or previous diagnosis of gestational diabetes or pre-baseline HbA1C ≥6.5%
• Requiring initial sequential or parallel therapy with immunosuppressive antibody preparation(s).
• Requiring ongoing dosing with a systemic immunosuppressive drug prior to transplantation (e.g. for Lupus Disease, FSGN etc) other than minimal levels of immunosuppressant following failure of a previous transplantation without nephrectomy
• Where Physician considers long term steroid treatment is necessary for the prevention of recurrent auto immune mediated renal disease or if the subject requires ongoing dosing with corticosteroids during the study for any other condition
• Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer
• Pregnant woman or breast-feeding mother
• Subject or donor known to be HIV positive
• Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, basiliximab, mycophenolate mofetil or any of the product excipients
• Evidence of malignant disease within the last 5 years other than Basal Cell Carcinoma or Squamous Cell Carcinoma
• Currently participating in another clinical trial and/or has taken an investigational drug within 28 days prior to randomization
• Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator
• Unlikely to comply with the visits scheduled in the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 10 Days of Steroids; Advagraf + Basiliximab + MMF + Steroids (10 days)	Drug: Mycophenolate Mofetil; oral; Other Names: CellCept; Drug: Advagraf; oral; Other Names: FK506E; modified release tacrolimus; Drug: Simulect; IV; Other Names: Basiliximab; Drug: Corticosteroids; IV & oral; Other Names: prednisolone; methylprednisolone
Experimental: Optional Steroid bolus only; Advagraf + Basiliximab + MMF + Steroids (bolus only)	Drug: Mycophenolate Mofetil; oral; Other Names: CellCept; Drug: Advagraf; oral; Other Names: FK506E; modified release tacrolimus; Drug: Simulect; IV; Other Names: Basiliximab; Drug: Corticosteroids; IV & oral; Other Names: prednisolone; methylprednisolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Diagnosis of new onset Diabetes Mellitus as per ADA criteria at any point up to 24 weeks after kidney transplantation	up to 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy failure using a composite endpoint consisting of graft loss, biopsy confirmed acute rejection or graft dysfunction	up to 6 months
Positive Oral Glucose Tolerance Test	8 weeks
Repeat Positive Oral Glucose Tolerance Test	6 months
Renal function	at 6 months
Acute Rejections	up to 6 months
Biopsy confirmed acute rejections	up to 6 months
Subject survival	up to 6 months
Graft survival	up to 6 months
Change from Baseline in HbA1C levels	Baseline, week 12 and week 24

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Use Central Contact, Astellas Pharma Europe Ltd.

Publications and helpful links

General Publications

• Mourad G, Glyda M, Albano L, Viklicky O, Merville P, Tyden G, Mourad M, Lohmus A, Witzke O, Christiaans MHL, Brown MW, Undre N, Kazeem G, Kuypers DRJ; Advagraf-based immunosuppression regimen examining new onset diabetes mellitus in kidney transplant recipients (ADVANCE) study investigators. Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial. Transplantation. 2017 Aug;101(8):1924-1934. doi: 10.1097/TP.0000000000001453.

Helpful Links

• Link to results on the Astellas Clinical Study Results website.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2011
• Primary Completion (Actual): May 22, 2013
• Study Completion (Actual): May 22, 2013

Study Registration Dates

• First Submitted: February 3, 2011
• First Submitted That Met QC Criteria: February 25, 2011
• First Posted (Estimated): February 28, 2011

Study Record Updates

• Last Update Posted (Actual): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Immunosuppression; Diabetes Mellitus; Transplant; Kidney
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Protective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Neuroprotective Agents; Calcineurin Inhibitors; Basiliximab; Prednisolone; Mycophenolic Acid; Methylprednisolone; Tacrolimus
• Other Study ID Numbers: PMR-EC-1211; 2010-019638-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR