European Trial of Immunosuppression in SPK Tx

A European Multicenter Open-Label Randomised Trial to Evaluate the Efficacy and Safety of Sirolimus and Tacrolimus Compared to MMF and Tacrolimus With Short-Course Induction Therapy, Short-Term Steroids Application in de Novo SPK Transplanted Diabetic Patients

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.

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.

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.

    -