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

Astellas

Status and phase: Completed; Phase 4

Conditions: Kidney Transplantation

Treatments: Drug: Corticosteroids; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Drug: Advagraf

Study type: Interventional

Funder types: Industry

Identifiers

NCT01363752

2010-019639-37 (EudraCT Number)

PMR-EC-1212

Details and patient eligibility

About

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

Full 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.

Enrollment: 853 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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853 participants in 2 patient groups

Advagraf + MMF + Steroids

Active Comparator group

Description:

Without sirolimus

Treatment:

Drug: Advagraf

Drug: Corticosteroids

Drug: Mycophenolate Mofetil

Advagraf + MMF + Steroids + Sirolimus

Experimental group

Description:

With sirolimus; MMF withdrawn on Day 28; Sirolimus introduced on Day 28

Treatment:

Drug: Advagraf

Drug: Sirolimus

Drug: Corticosteroids

Drug: Mycophenolate Mofetil