Calcineurin Free Immunosuppression in Renal Transplant Recipients

NCT00812123 | Completed Phase 4

• 1 other identifier: Calfree
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Transplantation; Chronic Kidney Disease

Keywords

kidney transplantation; calcineurin inhibitor free; protocol biopsy; Cyclosporin A; Sirolimus

Outcome Measures

Primary Outcomes (1)

• Plasma Creatinine

  6 months

Secondary Outcomes (4)

• 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

Study Arms (2)

Calcineurin free

EXPERIMENTAL

Immunosuppression with Sirolimus, Mycophenolate and Steroids

Drug: Sirolimus; Drug: Prednisone; Drug: Mycophenolate mofetil; Procedure: Protocol biopsies

Calcineurin

ACTIVE COMPARATOR

Immunosuppressive therapy with Cyclosporin A, Mycophenolate and Steroids

Drug: Cyclosporine A; Drug: Prednisone; Drug: Mycophenolate mofetil; Procedure: Protocol biopsies

Interventions

Sirolimus DRUG

Loading dose 30 mg for three days, trough level of 10-20 ng/ml month 1-3, 8-15 ng/ml month 4 - 6

Also known as: Rapamune

Calcineurin free

Cyclosporine A DRUG

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

Also known as: Sandimmun neoral

Calcineurin

Prednisone DRUG

0.5 mg/kg, tapering every two weeks until 0.1 mg/kg

Calcineurin; Calcineurin free

Mycophenolate mofetil DRUG

2 x 1000mg, through level above 2ug/ml

Also known as: CellCept

Calcineurin; Calcineurin free

Protocol biopsies PROCEDURE

protocol kidney biopsies at month one and three

Calcineurin; Calcineurin free

Eligibility Criteria

• Age: 15 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (1)

University Hospital Basel, Clinic for Transplantation Immunology and Nephrology

Basel, 4031, Switzerland

Location

Related Publications (1)

• Franz S, Regeniter A, Hopfer H, Mihatsch M, Dickenmann M. Tubular toxicity in sirolimus- and cyclosporine-based transplant immunosuppression strategies: an ancillary study from a randomized controlled trial. Am J Kidney Dis. 2010 Feb;55(2):335-43. doi: 10.1053/j.ajkd.2009.09.004. Epub 2009 Nov 17.

  PMID: 19926370 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Sirolimus; Cyclosporine; Prednisone; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Jürg U Steiger, MD

  Clinic for Transplantation Immunology and Nephrology, University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 18, 2008
• First Posted: December 19, 2008
• Study Start: January 1, 2001
• Primary Completion: July 1, 2005
• Study Completion: July 1, 2005
• Last Updated: December 19, 2008

Record last verified: 2008-12

Locations

CH (1)