Clinical trial NCT01363752: A Study Looking at Kidney Function in Kidney Transplant Recipients Who Are Taking Anti-rejection Medication Including Tacrolimus and With or Without Sirolimus.
Official title: A Multicenter, Two Arm, Randomized, Open Label Clinical Study Investigating Renal Function in an Advagraf® Based Immunosuppressive Regimen With or Without Sirolimus in Kidney Transplant Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplantation
Keywords: Kidney
Kidney Failure, Acute
Astagraf XL
Immunosuppression
Advagraf
Tacrolimus
Transplant
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2011-06-02
Enrollment: 853
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 compare the effect of two anti-rejection therapy regimens on kidney function in kidney transplant recipients.

Detailed description: This study will evaluate the potential to reduce nephrotoxic calcineurin inhibitors (CNI) therapy by lowering tacrolimus exposure from Advagraf® in combination with the non-nephrotoxic immunosuppressant sirolimus to avoid the risk of acute graft rejection, compared with an Advagraf® and Mycophenolate Mofetil (MMF) immunosuppressive regimen.

Eligibility criteria: Inclusion Criteria:

* End stage kidney disease and a suitable candidate for primary renal transplantation or re-transplantation (unless the graft was lost from rejection within 6 months)
* Receiving a kidney transplant from a deceased or living (non Human Leukocyte Antigen \[HLA\] identical) donor with compatible ABO blood type
* Female subject of childbearing potential has a negative serum or urine pregnancy test at enrollment
* Female and male subjects agree to maintain highly effective birth control during the study and for 90 days after discontinuation of dosing with study drugs. 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 Intrauterine Devises (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 (PRA) \>20%
* 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
* Requiring initial sequential or parallel therapy with immunosuppressive antibody preparation(s)
* Requiring ongoing dosing with a systemic immunosuppressive drug prior to transplantation (other than minimal levels of immunosuppression following failure of previous transplantation without nephrectomy)
* 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, sirolimus, MMF or any of the product excipients or iodine
* Evidence of malignant disease within the last 5 years, not including non-malignant skin cancers
* Currently participating in another clinical trial, and/ or has taken an investigational drug within 28 days prior to enrollment
* Unlikely to comply with the visits scheduled in the protocol

Primary outcomes:
measure: Glomerular Filtration Rate (GFR) estimated by iohexol clearance at Week 52 post kidney transplantation
timeFrame: up to 1 year
Secondary outcomes:
measure: Efficacy failure
timeFrame: up to 1 year
measure: GFR at Week 52 post kidney transplantation by Modification Diet in Renal Disease (MDRD) formula
timeFrame: up to 1 year
measure: GFR at Week 52 post kidney transplantation by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
timeFrame: up to 1 year
measure: Calculated creatinine clearance at Week 52 post kidney transplantation by Cockcroft and Gault formula
timeFrame: up to 1 year
measure: Incidence of clinical acute rejection
timeFrame: up to 1 year
measure: Time to clinical acute rejection
timeFrame: up to 1 year
measure: Incidence of Biopsy Confirmed Acute Rejection
timeFrame: up to 1 year
measure: Time to Biopsy Confirmed Acute Rejection
timeFrame: up to 1 year
measure: Subject survival
timeFrame: up to 1 year
measure: Graft survival
timeFrame: up to 1 year
measure: New Onset Diabetes Mellitus (NODM) as per American Diabetic Association (ADA) criteria
timeFrame: up to 1 year
Other outcomes:
Locations:
city: New Lambton
country: Australia
facility: 5042
city: Perth
country: Australia
facility: 5043
city: Innsbruck
country: Austria
facility: 1141
city: Linz
country: Austria
facility: 1142
city: Vienna
country: Austria
facility: 1140
city: Minsk
country: Belarus
facility: 3240
city: Leuven
country: Belgium
facility: 1241
city: Liege 1
country: Belgium
facility: 1240
city: Brno
country: Czechia
facility: Site 1441
city: Ostrava - Poruba
country: Czechia
facility: 1440
city: Amiens Cedex
country: France
facility: 1752
city: Brest Cedex 2
country: France
facility: 1740
city: Clermont-Ferrand Cedex 1
country: France
facility: 1742
city: Creteil Cedex
country: France
facility: 1746
city: Dijon
country: France
facility: 1750
city: Le Kremilin Bicetre Cedex
country: France
facility: 1741
city: Paris Cedex 15
country: France
facility: 1749
city: Toulouse Cedex 9
country: France
facility: 1751
city: Tours cedex 9
country: France
facility: 1748
city: Vandoeuvre Les Nancy Cedex
country: France
facility: 1745
city: Bochum
country: Germany
facility: 1541
city: Erlangen
country: Germany
facility: 1542
city: Essen
country: Germany
facility: 1543
city: Frankfurt
country: Germany
facility: 1544
city: Hann.Munden
country: Germany
facility: 1545
city: Hannover
country: Germany
facility: 1540
city: Heidelberg
country: Germany
facility: 1546
city: Kiel
country: Germany
facility: 1547
city: Leipzig
country: Germany
facility: 1548
city: Munchen
country: Germany
facility: 1549
city: Munster
country: Germany
facility: 1550
city: Hong Kong
country: Hong Kong
facility: 5441
city: Budapest
country: Hungary
facility: 1940
city: Palermo
country: Italy
facility: 2144
city: Roma
country: Italy
facility: 2143
city: Siena
country: Italy
facility: 2140
city: Busan
country: Korea, Republic of
facility: 5245
city: Daegu
country: Korea, Republic of
facility: 5243
city: Seoul
country: Korea, Republic of
facility: 5242
city: Seoul
country: Korea, Republic of
facility: 5241
city: Seoul
country: Korea, Republic of
facility: 5244
city: Maastricht
country: Netherlands
facility: 2440
city: Katowice
country: Poland
facility: 2643
city: Lodz
country: Poland
facility: 2640
city: Poznan
country: Poland
facility: 2641
city: Kemerovo
country: Russian Federation
facility: 2841
city: Moscow
country: Russian Federation
facility: 2843
city: Omsk
country: Russian Federation
facility: 2842
city: Vol'ginskiy
country: Russian Federation
facility: 2840
city: Alicante
country: Spain
facility: 1640
city: Barcelona
country: Spain
facility: 1641
city: Santander
country: Spain
facility: 1643
city: Vizcaya
country: Spain
facility: 1642
city: Tainan
country: Taiwan
facility: 5343
city: Taoyuan
country: Taiwan
facility: 5342
city: Istanbul
country: Turkey
facility: 3042
city: Istanbul
country: Turkey
facility: 3043
city: Istanbul
country: Turkey
facility: 3044
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Use Central Contact
role: STUDY_DIRECTOR
References: