Calcineurin Free Immunosuppression in Renal Transplant Recipients - Full Text View

Sponsors and Collaborators:	University Hospital, Basel, Switzerland Wyeth Pharmaceuticals AG, Switzerland
Information provided by:	University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:	NCT00812123

Purpose

The main purpose of this study is to obtain preliminary information on the efficacy, safety and cost of two regimens, Rapamycin / MMF / steroid therapy and Cyclosporine A Neoral / MMF / steroid therapy, used in the prevention of acute rejection following renal transplantation.

Condition	Intervention	Phase
Kidney Transplantation Chronic Kidney Disease	Drug: Sirolimus Drug: Cyclosporine A Drug: Prednisone Drug: Mycophenolate mofetil Procedure: Protocol biopsies	Phase IV

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Prednisone Cyclosporin Cyclosporine Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Sirolimus

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Open, Single Center, Randomised, Parallel Group Pilot Study to Investigate a Calcineurin Free Immunosuppressive Treatment for de Novo Renal Transplant Recipients: A Comparison of a Rapamycin/MMF/Steroids Regime to a Cyclosporine A Neoral/MMF/Steroids Regimen in the Prevention of Acute Rejection Following Renal Transplantation

Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:

Plasma Creatinine [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Graft survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Patient survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Incidence of first acute rejections and number of total rejections [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Total number of anti-rejection treatments [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment:	127
Study Start Date:	January 2001
Study Completion Date:	July 2005
Primary Completion Date:	July 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Calcineurin free: Experimental Immunosuppression with Sirolimus, Mycophenolate and Steroids	Drug: Sirolimus Loading dose 30 mg for three days, trough level of 10-20 ng/ml month 1-3, 8-15 ng/ml month 4 - 6 Drug: Prednisone 0.5 mg/kg, tapering every two weeks until 0.1 mg/kg Drug: Mycophenolate mofetil 2 x 1000mg, through level above 2ug/ml Procedure: Protocol biopsies protocol kidney biopsies at month one and three
Calcineurin: Active Comparator Immunosuppressive therapy with Cyclosporin A, Mycophenolate and Steroids	Drug: Cyclosporine A Loading dose of 300 mg for three days, trough levels 250-300 ng/ml months 1-3, 150-250 ng/ml months 4 to 6 Drug: Prednisone 0.5 mg/kg, tapering every two weeks until 0.1 mg/kg Drug: Mycophenolate mofetil 2 x 1000mg, through level above 2ug/ml Procedure: Protocol biopsies protocol kidney biopsies at month one and three

Detailed Description:

This pilot study is designed to show differences in efficacy, safety and cost between the two regimens. Its main purpose is to provide information, if calcineurin free immunosuppressive treatment is a valuable alternative in the treatment of de novo kidney transplant recipients. Furthermore, by investigating the side effects in both arms it will be possible to decide, if the absence of calcineurin inhibition and lack of nephrotoxicity will outweigh the adverse effects of Rapamycin. With the obtained information it will be possible to plan a larger trial, which is warranted to compare the mentioned treatment regimens in more detail.

Eligibility

Ages Eligible for Study:	15 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female patients between 15 and 75 years of age, regardless of race.
Female patients of child bearing age agree to maintain effective birth control practice during the study.
Patient has end stage kidney disease and is a suitable candidate for primary renal transplantation or retransplantation as assessed by the transplantation center.
Patient has been fully informed and has given written or independent person witnessed oral informed consent.

Exclusion Criteria:

Patient is pregnant or breastfeeding.
Patient has a low immunological risk constellation, defined by receiving a kidney from a HLA-identical related living donor.
Patient has a high immunological risk constellation, defined as having within the previous three years a measured PRA grade of ≥25% and/or having a previous graft survival shorter than 3 years due to rejection.
Patient and donor have a positive T or B-cell crossmatch.
Patient and donor are ABO incompatible.
Age of donor > 68 years.
Cold ischemia time > 36 hours.
Patient has leucopenia, defined as having at transplantation less than 3000/mm3 leukocytes.
Patient has thrombocytopenia, defined as having at transplantation less than 75000/mm3 thrombocytes.
Patient is allergic or intolerant to cremophor RH 60 or structurally related compounds, steroids, Cyclosporine A Neoral, Rapamycin or MMF.
Patient requires initial sequential or parallel therapy with immunosuppressive antibody preparation(s).
Patient or donor is known to be HIV positive.
Patient has significant liver disease, defined as having during the past 28 days continuously ASAT (SGOT) and/or ALAT (SGPT) levels greater than 3 fold of the upper value of the normal range of the investigational site.
Patient with malignancy or history of malignancy ≥ 2 years, except non metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
Patient has significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, or active peptic ulcer.
Patient is taking or has been taking an investigational drug in the past 28 days.
Patient has previously received or is receiving another organ transplant other than kidney.
Patient is unlikely to comply with the visits schedule in the protocol.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00812123

Locations

Switzerland
University Hospital Basel, Clinic for Transplantation Immunology and Nephrology
Basel, Switzerland, 4031

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Wyeth Pharmaceuticals AG, Switzerland

Investigators

Principal Investigator:

Jürg U Steiger, MD

Clinic for Transplantation Immunology and Nephrology, University Hospital, Basel, Switzerland

More Information

Responsible Party:	University Hospital Basel, Switzerland ( Prof. Dr. J. Steiger )
Study ID Numbers:	Calfree
Study First Received:	December 18, 2008
Last Updated:	December 18, 2008
ClinicalTrials.gov Identifier:	NCT00812123
Health Authority:	Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:

kidney transplantation
calcineurin inhibitor free
protocol biopsy
Cyclosporin A
Sirolimus

Study placed in the following topic categories:

Sirolimus
Prednisone
Renal Insufficiency
Cyclosporine
Clotrimazole
Miconazole
Tioconazole

Kidney Failure, Chronic
Cyclosporins
Urologic Diseases
Renal Insufficiency, Chronic
Mycophenolate mofetil
Kidney Diseases
Kidney Failure

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Antineoplastic Agents, Hormonal
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Enzyme Inhibitors
Antibiotics, Antineoplastic

Immunosuppressive Agents
Glucocorticoids
Hormones
Pharmacologic Actions
Anti-Bacterial Agents
Antifungal Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on January 13, 2009