Clinical trial NCT00140543: European Trial of Immunosuppression in SPK Tx
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Diabetic Nephropathy
Keywords: simultaneous pancreas/kidney transplantation
Immunosuppression
Lead sponsor: EUROSPK Study Group
Sponsor class: OTHER
Collaborators: name: Fujisawa GmbH
name: Hoffmann-La Roche
name: Wyeth is now a wholly owned subsidiary of Pfizer
name: Neovii Biotech
name: Genzyme, a Sanofi Company
First posted: 2005-09-01
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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Primary outcomes:
measure: At 1 year:Incidence of biopsy-proven (kidney) rejection episodes.
Secondary outcomes:
measure: SECONDARY ENDPOINTS: At 6 months and 1 year
measure: * Kidney/Pancreas function (at 6 months and 1 year):
measure: - Kidney function will be measured by:
measure: - S- creatinine
measure: - Creatinine clearance
measure: - Pancreas function will be measured by:
measure: - Fasting Glucose level (< 123 mg/dl)
measure: - HbA1C
measure: - Need for insulin therapy
measure: - Need for oral drugs
measure: * At 6 months and 1 year:
measure: - Patient and graft survival
measure: - Lipid profile
measure: - Infections
measure: - Side effects
measure: - Blood Pressure
measure: - Treatment failure for any reason, such as permanent discontinuation of a drug, graft loss or death.
measure: * % of steroid free patients: at 6 months and 1 year.
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Universitätsklinik
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Prague
country: Czechia
facility: Institute for clinical and experimental medicine-IKEM
city: Berlin
country: Germany
facility: Charite Campus Virchow Klinikum
city: Bochum-Langendreer
country: Germany
facility: Knappschaftskrankenhaus
city: Frankfurt am Main
country: Germany
facility: Goethe University
city: Freiburg
country: Germany
facility: Chirurgische Universitätsklinik
city: Munich
country: Germany
facility: Klinikum Grosshadern-University of Munich
city: Munich
country: Germany
facility: Klinikum Innenstadt der Universität München
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Barcelona
country: Spain
facility: Hospital Clinico
city: Geneva
country: Switzerland
facility: Hôpital Cantonal de Geneve
Study officials:
affiliation: SPEAKER FOR THE EUROSPK STUDY GROUP
name: Jean-Paul Squifflet, MD,PhD
role: STUDY_CHAIR
References: