Calcineurin Free Immunosuppression in Renal Transplant Recipients

Phase 4

Completed

• Conditions: Kidney Transplantation; Chronic Kidney Disease
• Interventions: Drug: Cyclosporine A; Drug: Sirolimus; Drug: Prednisone; Drug: Mycophenolate mofetil; Procedure: Protocol biopsies

• Registration Number: NCT00812123
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2001-01
• Primary Completion: 2005-07
• Study Completion: 2005-07
• Status Verified: 2008-12
• Study First Submitted: 2008-12-18
• Study First Submitted QC: 2008-12-18
• Last Update Submitted: 2008-12-18
• Study First Posted: 2008-12-19
• Last Update Posted: 2008-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 127

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Calcineurin	Protocol biopsies	Immunosuppressive therapy with Cyclosporin A, Mycophenolate and Steroids
Calcineurin free	Protocol biopsies	Immunosuppression with Sirolimus, Mycophenolate and Steroids
Calcineurin	Cyclosporine A	Immunosuppressive therapy with Cyclosporin A, Mycophenolate and Steroids
Calcineurin	Prednisone	Immunosuppressive therapy with Cyclosporin A, Mycophenolate and Steroids
Calcineurin free	Prednisone	Immunosuppression with Sirolimus, Mycophenolate and Steroids
Calcineurin free	Sirolimus	Immunosuppression with Sirolimus, Mycophenolate and Steroids
Calcineurin free	Mycophenolate mofetil	Immunosuppression with Sirolimus, Mycophenolate and Steroids
Calcineurin	Mycophenolate mofetil	Immunosuppressive therapy with Cyclosporin A, Mycophenolate and Steroids

Primary Outcome Measures

Name	Time	Method
Plasma Creatinine	6 months

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

University Hospital Basel, Clinic for Transplantation Immunology and Nephrology; 🇨🇭 Basel, Switzerland