Calcineurin Free Immunosuppression in Renal Transplant Recipients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00812123
Recruitment Status : Completed
First Posted : December 19, 2008
Last Update Posted : December 19, 2008
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:
University Hospital, Basel, Switzerland

Brief Summary:
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 or disease Intervention/treatment Phase
Kidney Transplantation Chronic Kidney Disease Drug: Sirolimus Drug: Cyclosporine A Drug: Prednisone Drug: Mycophenolate mofetil Procedure: Protocol biopsies Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 127 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2001
Actual Primary Completion Date : July 2005
Actual Study Completion Date : July 2005

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Calcineurin free
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
Other Name: Rapamune

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
Other Name: CellCept

Procedure: Protocol biopsies
protocol kidney biopsies at month one and three

Active Comparator: Calcineurin
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
Other Name: Sandimmun neoral

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
Other Name: CellCept

Procedure: Protocol biopsies
protocol kidney biopsies at month one and three

Primary Outcome Measures :
  1. Plasma Creatinine [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Graft survival [ Time Frame: 6 months ]
  2. Patient survival [ Time Frame: 6 months ]
  3. Incidence of first acute rejections and number of total rejections [ Time Frame: 6 months ]
  4. Total number of anti-rejection treatments [ Time Frame: 6 months ]

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Ages Eligible for Study:   15 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00812123

University Hospital Basel, Clinic for Transplantation Immunology and Nephrology
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Wyeth is now a wholly owned subsidiary of Pfizer
Principal Investigator: Jürg U Steiger, MD Clinic for Transplantation Immunology and Nephrology, University Hospital, Basel, Switzerland

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Prof. Dr. J. Steiger, University Hospital Basel, Switzerland Identifier: NCT00812123     History of Changes
Other Study ID Numbers: Calfree
First Posted: December 19, 2008    Key Record Dates
Last Update Posted: December 19, 2008
Last Verified: December 2008

Keywords provided by University Hospital, Basel, Switzerland:
kidney transplantation
calcineurin inhibitor free
protocol biopsy
Cyclosporin A

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Mycophenolic Acid
Immunosuppressive Agents
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Anti-Bacterial Agents
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents