An Open, Single Centre, Randomised, Parallel Group Study to Investigate Three Different Immunosuppressive Regimens (SterFreePlus)

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by:
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT01183247
First received: August 16, 2010
Last updated: NA
Last verified: August 2010
History: No changes posted
  Purpose

An open, single center, randomised study to investigate three different immunosuppressive regimens for de novo renal transplant recipients:

  1. st sirolimus / EC-MPS / tacrolimus regimen

    - After 3 months a protocol biopsy is performed. If no rejection is detected the calcineurin inhibitor (tacrolimus) is withdrawn.

  2. nd everolimus / EC-MPS / tacrolimus regimen

    - After 3 months a protocol biopsy is performed. If no rejection is detected the calcineurin inhibitor (tacrolimus) is withdrawn.

  3. rd tacrolimus / EC-MPS / prednisone regimen - After 3 months a protocol biopsy is performed. If no rejection is detected prednisone is withdrawn.

Condition Intervention Phase
Comparative Study
Immunosuppressive Agents
Drug: Rapamycin
Drug: Everolimus
Drug: Prednisone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open, Single Centre, Randomised, Parallel Group Study to Investigate Three Different Immunosuppressive Regimens for de Novo Renal Transplant Recipients: A Comparison of a Sirolimus / EC-MPS (Myfortic) / Tacrolimus Regimen, an Everolimus / EC-MPS / Tacrolimus Regimen and a EC-MPS / Tacrolimus Prednisone Regimen

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Plasma creatinine and creatinine clearance (Cockcroft-Gault) after 6 months of treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: July 2008
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rapamycin
Rapamycin-MMF-tacrolimus
Drug: Rapamycin
Add rapamycin de novo to tacrolimus and MMF
Other Name: Sirolimus
Active Comparator: Everolimus
Everolimus - tacrolimus - MMF
Drug: Everolimus
Add everolimus de novo to tacrolimus and MMF
Active Comparator: Prednisone
tacrolimus - MMF -prednisone
Drug: Prednisone
Add prednisone de novo to tacrolimus and MMF

Detailed Description:

This study is designed to show similar efficacy but a different adverse event profile between the three regimens. Its main purpose is to provide more information, if steroid free immunosuppressive treatment is a valuable alternative in the treatment of de novo kidney transplant recipients and that it is possible to withdraw calcineurin inhibitors after 3 months in this steroid free protocol. A secondary rationale of the study is to compare sirolimus with everolimus directly to better differentiate these two mTOR-inhibitors in terms of compound-specific effects and class-effects. This should allow for early conclusions on the usage of these two mTOR-inhibitors in CNI-free regimens.

Basis for this study are the following hypotheses regarding the first 6 months of treatment following kidney transplantation:

  • Similar graft function in the three treatment groups after 6 months
  • No difference in graft and patient survival in the three groups
  • No differences in incidence of first, total number, type of acute rejections, and number of anti-rejection treatments in the three groups
  • No differences in number of patients successfully withdrawn from calcineurin inhibitor in the sirolimus and everolimus arm, respectively
  • A different adverse event profile with regard to the incidence of dyslipidemias, impaired fasting glucose, new onset diabetes mellitus, de novo post-transplant insulin dependency, histological signs of calcineurin inhibitor toxicity, and tubulointerstitial nephrotoxicity in the three groups. In addition to this the incidence of mTOR-inhibitor specific adverse events will be analysed.

These hypotheses are the basis for the study objectives.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients between 18 and 75 years of age, regardless of race.
  2. Female patients of child bearing age agree to maintain effective birth control practice during the study.
  3. Patient has end stage kidney disease and is a suitable candidate for primary renal transplantation or retransplantation as assessed by the transplantation centre.
  4. Patient has been fully informed and has given written or independent person witnessed oral informed consent.

Exclusion Criteria:

  1. in Patient is pregnant or breastfeeding.
  2. Patient has a low immunological risk constellation, defined by receiving a kidney from a HLA-identical related living donor.
  3. Patient has a high immunological risk constellation, defined as having donor specific HLA-antibodies and/or having a previous graft survival shorter than 3 years due to rejection.
  4. Patient and donor have a positive T or B-cell crossmatch.
  5. Patient and donor are ABO incompatible.
  6. Age of donor > 75 years.
  7. Cold ischemia time > 36 hours.
  8. Patient has leucopenia, defined as having at transplantation less than 3000/mm3 leukocytes.
  9. Patient has thrombocytopenia, defined as having at transplantation less than 75000/mm3 thrombocytes.
  10. Patient is allergic or intolerant to cremophor RH 60 or structurally related compounds, steroids, everolimus, tacrolimus, Sirolimus or EC-MPS.
  11. Patient or donor is known to be HIV positive.
  12. 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.
  13. 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.
  14. Patient has significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, or active peptic ulcer.
  15. Patient is taking or has been taking an investigational drug in the past 28 days.
  16. Patient has previously received or is receiving another organ transplant other than kidney.
  17. Patient is unlikely to comply with the visits schedule the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01183247

Locations
Switzerland
Clinic for transplantation immunology and nephrology
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Novartis
Investigators
Principal Investigator: Juerg U Steiger, Professor University Hospital, Basel, Switzerland
  More Information

No publications provided

Responsible Party: Juerg Steiger, professor, clinic for transplantation immunology and nephrology, university hospital Basel
ClinicalTrials.gov Identifier: NCT01183247     History of Changes
Other Study ID Numbers: 187/07
Study First Received: August 16, 2010
Last Updated: August 16, 2010
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
Everolimus,
rapamycin,
prednisone,
tacrolimus,
MMF,
steroid-free,
protocol biopsy

Additional relevant MeSH terms:
Immunosuppressive Agents
Sirolimus
Everolimus
Tacrolimus
Prednisone
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 24, 2014