Pilot Study to Investigate a Steroid Free Immunosuppressive Regimen for Renal Transplant Recipients

Study Overview
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Brief Summary
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The main purpose of this study is to investigate, whether a steroid free immunosuppressive treatment is a valuable alternative in the treatment of de novo kidney transplant recipients and if it is possible to withdraw calcineurin inhibitors after 3 months.

Detailed Description
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Protocol synopsis Title An open, single centre, pilot study to investigate a steroid free immunosuppressive regimen for de novo renal transplant recipients followed by a two arm randomization to a calcineurin inhibitor containing and a calcineurin inhibitor free maintenance immunosuppression after three months. Study code Sterfree pilot study Project phase An open, single centre, one arm study followed by a 1:1 randomized, parallel group, comparative study after three months. Study objectives To obtain preliminary information on the efficacy and safety of a rapamycin / sodium-mycophenolate (Myfortic) / tacrolimus regimen in the absence of steroids for the prevention of acute rejection following renal transplantation. To compare a low dose tacrolimus / rapamycin / sodium-mycophenolate (Myfortic) regimen to a rapamycin / sodium-mycophenolate regimen in patients without evidence of acute rejection after three months. Efficacy: Primary endpoint Plasma creatinine (and creatinine clearance (Cockcroft)) Secondary endpoints Incidence of first acute rejections and total number of acute rejections Total number of anti-rejection treatments Patients successfully withdrawn from calcineurin inhibitor at three months Graft survival Patient survival Safety: Graft survival Patient survival Protocol biopsies at 3 months( range: day 75 to 105) and 6 months (range day 165 to 195) sub clinical rejection Incidence of first acute biopsy proven rejection and total number of acute rejection episodes Total number of anti-rejection treatments Patients switched from assigned therapy due to rejection or side effects Patients needing steroids because of rejection Incidence of selected adverse events: tubulointerstitial nephrotoxicity (TOR inhibitor), leucopenia, thrombocytopenia, elevated fasting blood glucose, dyslipidemia, , electrolyte disturbances, de novo insulin dependency, gastrointestinal disorders (non infectious), neurotoxicity. Patients withdrawn due to adverse events Long term patient follow up Patients will be followed up for graft and patient survival at 12, 24, and 36 months post-transplantation.

Official Title
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Open, Single Centre, Pilot Study to Investigate a Steroid Free Immunosuppressive Regimen for De Novo Renal Transplant Recipients Followed by Randomisation to Calcineurin Inhibitor Containing or Calcineurin Inhibitor Free Immunosuppression

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Rapamycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients with end stage kidney disease suitable for primary renal transplantation or retransplantation patients receiving a graft from a living related, living unrelated or brain-death donor Exclusion Criteria: patients with a low or high immunological risk constellation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Rapamycin - MMF after 3 months | Drug: Rapamycin<br>* Sirolimus perorally following kidney transplantation, randomisation after protocol biopsy at months three to a) Sirolimus - MF- or b) low dose tacrolimus - sirolimus -MMF -<br>* Other names: Rapammune;|
| Active Comparator: B<br>Low dose tacrolimus - MMF - Rapamycin after 3 months | Drug: Rapamycin<br>* Sirolimus perorally following kidney transplantation, randomisation after protocol biopsy at months three to a) Sirolimus - MF- or b) low dose tacrolimus - sirolimus -MMF -<br>* Other names: Rapammune;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Allograft function |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients successfully withdrawn from calcineurin inhibitor after three months |  | 3 months | 
| Graft survival |  | 6 months | 
| Patient survival |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplantation, Steroid free, Calcineurin inhibitor free, Tacrolimus, Sirolimus