Calcineurin Free Immunosuppression in Renal Transplant Recipients

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Completed

CT.gov ID

NCT00812123

Collaborator

Wyeth is now a wholly owned subsidiary of Pfizer (Industry)

127

Enrollment

Location

Arms

53.9

Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

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 :

Jan 1, 2001

Actual Primary Completion Date :

Jul 1, 2005

Actual Study Completion Date :

Jul 1, 2005

Arms and Interventions

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

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 Names:

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 Names:

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 Names:

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 Names:

CellCept

Procedure: Protocol biopsies

protocol kidney biopsies at month one and three

Outcome Measures

Primary Outcome Measures

Plasma Creatinine [6 months]

Secondary Outcome Measures

Graft survival [6 months]
Patient survival [6 months]
Incidence of first acute rejections and number of total rejections [6 months]
Total number of anti-rejection treatments [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.