Calcineurin Free Immunosuppression in Renal Transplant Recipients

Chronic Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00812123
• Other study ID #: Calfree
• Status: Completed
• Phase: Phase 4
• First received: December 18, 2008
• Last updated: December 18, 2008
• Start date: January 2001
• Est. completion date: July 2005

Study information

• Verified date: December 2008
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: July 2005
• Est. primary completion date: July 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Kidney Transplantation
• Renal Insufficiency, Chronic

Intervention

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
• 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
• Prednisone
0.5 mg/kg, tapering every two weeks until 0.1 mg/kg
• Mycophenolate mofetil
2 x 1000mg, through level above 2ug/ml

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

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Clinic for Transplantation Immunology and Nephrology	Basel

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Creatinine		6 months	No
Secondary	Graft survival		6 months	No
Secondary	Patient survival		6 months	No
Secondary	Incidence of first acute rejections and number of total rejections		6 months	No
Secondary	Total number of anti-rejection treatments		6 months	No