Diabetes Mellitus, Type 1, Diabetic Nephropathy
Conditions
Keywords
simultaneous pancreas/kidney transplantation, Immunosuppression
Brief summary
1. To determine and compare the efficacy of Tacrolimus/Rapa versus Tacrolimus/MMF-based immunosuppression (in conjunction with initial short-term steroids and polyclonal antibody administration) in Type 1-diabetic patients undergoing simultaneous pancreas/kidney allograft transplantation. 2. To evaluate the safety of Tacrolimus/Rapa versus Tacrolimus/MMF in terms of drug-related complications and overimmunosuppression-associated complications, particularly under monitoring of the pharmacokinetic profile of all drugs administered.
Detailed description
This will be a controlled, randomised study, to be performed in 15-20 pancreas transplantation centers throughout Europe. Patients will be randomised into one of two treatment groups. Group 1 will receive Tacrolimus and Mycophenolate Mofetil (= best group in EuroSPK001 trial). Group 2 will receive Tacrolimus and Sirolimus. Both groups will receive in association short-term corticosteroids and polyclonal antibody preparation. Patients will be randomly assigned to one of the 2 treatment groups in a 1:1 ratio before transplantation. The study will last 3 years, with a first interim analysis of the data at 6 months and a complete analysis at 1 year.
Interventions
DRUGsirolimus versus mycophenolate mofetil
Sponsors
Fujisawa GmbH
Hoffmann-La Roche
Wyeth is now a wholly owned subsidiary of Pfizer
Neovii Biotech
Genzyme, a Sanofi Company
EUROSPK Study Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients, of 18 to 55 years of age, with end-stage, C-peptide-negative, Type 1-diabetic nephropathy. 2. Female patients of childbearing age must have a negative pregnancy test and must agree to maintain effective birth control practice throughout the study period (3 years). 3. Patient must have signed the Patient Informed Consent Form. 4. Patient must receive a primary simultaneous pancreas/kidney (SPK) cadaveric transplant, with either intestinal or bladder and either portal or systemic venous drainages.
Exclusion criteria
1. Patient is pregnant or breastfeeding. 2. Patient is allergic or intolerant to Mycophenolate Mofetil, Sirolimus, Tacrolimus or other macrolides, or any compounds structurally related to these compounds. 3. Patient has a positive T-cell crossmatch on the most recent serum specimen. 4. Patient is known for active liver disease or has significant liver disease, defined by ASAT and ALAT serum levels greater than 3 times the upper limit of normal. 5. Patient has malignancy or history of malignancy, with the exception of adequately treated localised squamous cell or basal cell carcinoma, without recurrence. 6. Patient has been included in another clinical trial protocol for any investigational drug within 4 weeks prior to randomisation. 7. Patient has any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, may invalidate communication. 8. Patient receives a SPK transplant from a living donor, or receives segmental pancreatic transplant, or a previous kidney transplant alone. 9. Pancreatic duct occlusion technique . 10. Donor is older than 55 years of age. \-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| At 1 year:Incidence of biopsy-proven (kidney) rejection episodes. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Kidney/Pancreas function (at 6 months and 1 year): | — |
| - Kidney function will be measured by: | — |
| - S- creatinine | — |
| - Creatinine clearance | — |
| - Pancreas function will be measured by: | — |
| - Fasting Glucose level (< 123 mg/dl) | — |
| - HbA1C | — |
| - Need for insulin therapy | — |
| SECONDARY ENDPOINTS: At 6 months and 1 year | — |
| * At 6 months and 1 year: | — |
| - Patient and graft survival | — |
| - Lipid profile | — |
| - Infections | — |
| - Side effects | — |
| - Blood Pressure | — |
| - Treatment failure for any reason, such as permanent discontinuation of a drug, graft loss or death. | — |
| * % of steroid free patients: at 6 months and 1 year. | — |
| - Need for oral drugs | — |
Countries
Austria, Belgium, Czechia, Germany, Israel, Spain, Switzerland
Outcome results
None listed