A Study Looking at Kidney Function in Kidney Transplant Recipients Who Are Taking Anti-rejection Medication Including Tacrolimus and With or Without Sirolimus.

Kidney Transplantation Clinical Trial

— ADHERE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01363752
• Other study ID #: PMR-EC-1212
• Secondary ID: 2010-019639-37
• Status: Completed
• Phase: Phase 4
• Start date: March 8, 2011
• Est. completion date: September 18, 2013

Study information

• Verified date: July 2018
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the effect of two anti-rejection therapy regimens on kidney function in kidney transplant recipients.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 853
• Est. completion date: September 18, 2013
• Est. primary completion date: September 18, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Advagraf
oral
• Mycophenolate Mofetil
oral
• Sirolimus
oral
• Corticosteroids
i.v. and oral

Locations

Country	Name	City	State
Australia	5042	New Lambton
Australia	5043	Perth
Austria	1141	Innsbruck
Austria	1142	Linz
Austria	1140	Vienna
Belarus	3240	Minsk
Belgium	1241	Leuven
Belgium	1240	Liege 1
Czechia	Site 1441	Brno
Czechia	1440	Ostrava - Poruba
France	1752	Amiens Cedex
France	1740	Brest Cedex 2
France	1742	Clermont-Ferrand Cedex 1
France	1746	Creteil Cedex
France	1750	Dijon
France	1741	Le Kremilin Bicetre Cedex
France	1749	Paris Cedex 15
France	1751	Toulouse Cedex 9
France	1748	Tours cedex 9
France	1745	Vandoeuvre Les Nancy Cedex
Germany	1541	Bochum
Germany	1542	Erlangen
Germany	1543	Essen
Germany	1544	Frankfurt
Germany	1545	Hann.Munden
Germany	1540	Hannover
Germany	1546	Heidelberg
Germany	1547	Kiel
Germany	1548	Leipzig
Germany	1549	Munchen
Germany	1550	Munster
Hong Kong	5441	Hong Kong
Hungary	1940	Budapest
Italy	2144	Palermo
Italy	2143	Roma
Italy	2140	Siena
Korea, Republic of	5245	Busan
Korea, Republic of	5243	Daegu
Korea, Republic of	5241	Seoul
Korea, Republic of	5242	Seoul
Korea, Republic of	5244	Seoul
Netherlands	2440	Maastricht
Poland	2643	Katowice
Poland	2640	Lodz
Poland	2641	Poznan
Russian Federation	2841	Kemerovo
Russian Federation	2843	Moscow
Russian Federation	2842	Omsk
Russian Federation	2840	Vol'ginskiy
Spain	1640	Alicante
Spain	1641	Barcelona
Spain	1643	Santander
Spain	1642	Vizcaya
Taiwan	5343	Tainan
Taiwan	5342	Taoyuan
Turkey	3042	Istanbul
Turkey	3043	Istanbul
Turkey	3044	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Countries where clinical trial is conducted

Australia,  Austria,  Belarus,  Belgium,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glomerular Filtration Rate (GFR) estimated by iohexol clearance at Week 52 post kidney transplantation		up to 1 year
Secondary	Efficacy failure	Composite endpoint defined as graft loss (re-transplantation, nephrectomy, death or dialysis ongoing at the study end) or subject withdrawal	up to 1 year
Secondary	GFR at Week 52 post kidney transplantation by Modification Diet in Renal Disease (MDRD) formula		up to 1 year
Secondary	GFR at Week 52 post kidney transplantation by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula		up to 1 year
Secondary	Calculated creatinine clearance at Week 52 post kidney transplantation by Cockcroft and Gault formula		up to 1 year
Secondary	Incidence of clinical acute rejection		up to 1 year
Secondary	Time to clinical acute rejection		up to 1 year
Secondary	Incidence of Biopsy Confirmed Acute Rejection		up to 1 year
Secondary	Time to Biopsy Confirmed Acute Rejection		up to 1 year
Secondary	Subject survival		up to 1 year
Secondary	Graft survival		up to 1 year
Secondary	New Onset Diabetes Mellitus (NODM) as per American Diabetic Association (ADA) criteria		up to 1 year

External Links

•   Link to results on the Astellas Clinical Study Results website