Clinical trial NCT01304836: A Study Looking at Diabetes in Kidney Transplant Recipients Receiving Immunosuppressive Regimen With or Without Steroids
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplantation
Keywords: Kidney
Diabetes Mellitus
Transplant
Immunosuppression
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2011-02-28
Enrollment: 1166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Diagnosis of new onset Diabetes Mellitus as per ADA criteria at any point up to 24 weeks after kidney transplantation
timeFrame: up to 6 months
Secondary outcomes:
measure: Efficacy failure using a composite endpoint consisting of graft loss, biopsy confirmed acute rejection or graft dysfunction
timeFrame: up to 6 months
measure: Positive Oral Glucose Tolerance Test
timeFrame: 8 weeks
measure: Repeat Positive Oral Glucose Tolerance Test
timeFrame: 6 months
measure: Renal function
timeFrame: at 6 months
measure: Acute Rejections
timeFrame: up to 6 months
measure: Biopsy confirmed acute rejections
timeFrame: up to 6 months
measure: Subject survival
timeFrame: up to 6 months
measure: Graft survival
timeFrame: up to 6 months
measure: Change from Baseline in HbA1C levels
timeFrame: Baseline, week 12 and week 24
Other outcomes:
Locations:
city: Perth
country: Australia
city: Sydney
country: Australia
city: Sydney
country: Australia
city: Brussels
country: Belgium
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Cali
country: Colombia
city: Brno
country: Czechia
city: Hradec Kralove
country: Czechia
city: Olomouc
country: Czechia
city: Prague
country: Czechia
city: Tartu
country: Estonia
city: Helsinki
country: Finland
city: Bordeaux
country: France
city: Cite Nord
country: France
city: D'Angers
country: France
city: Le Puytren
country: France
city: Montpellier
country: France
city: Nantes
country: France
city: Nice
country: France
city: Paris
country: France
city: Rennes
country: France
city: Rouen
country: France
city: Strasbourg
country: France
city: Suresnes
country: France
city: Aachen
country: Germany
city: Bonn
country: Germany
city: Düsseldorf
country: Germany
city: Essen
country: Germany
city: Halle Saale
country: Germany
city: Kaiserslautern
country: Germany
city: Mannheim
country: Germany
city: Muenchen
country: Germany
city: Regensburg
country: Germany
city: Rostock
country: Germany
city: Debrecen
country: Hungary
city: Szeged
country: Hungary
city: Ancona
country: Italy
city: Bologna
country: Italy
city: Cagliari
country: Italy
city: L'Aquila
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Padova
country: Italy
city: Pisa
country: Italy
city: Roma
country: Italy
city: Salerno
country: Italy
city: Treviso
country: Italy
city: Vicenza
country: Italy
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Riga
country: Latvia
city: Vilnius
country: Lithuania
city: Cuernavaca
country: Mexico
city: Mexico City
country: Mexico
city: Maastricht
country: Netherlands
city: Olso
country: Norway
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Poznan
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Bucharest
country: Romania
city: Lasi
country: Romania
city: Ekaterinburg
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhniy Novgorod
country: Russian Federation
city: Omsk
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Vol'skiy
country: Russian Federation
city: Banska Bystrica
country: Slovakia
city: Bratislava
country: Slovakia
city: Kosice
country: Slovakia
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Santa Cruz de Tenerife
country: Spain
city: Sevilla
country: Spain
city: Toledo
country: Spain
city: Valencia
country: Spain
city: Valladolid
country: Spain
city: Goteborg
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Bern
country: Switzerland
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Use Central Contact
role: STUDY_DIRECTOR
References:
citation: 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.