Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen (Allegro)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2012 by University Medical Centre Groningen
Sponsor:
Collaborators:
Leiden University Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Information provided by (Responsible Party):
J.S.F. Sanders, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01560572
First received: December 21, 2011
Last updated: March 22, 2012
Last verified: March 2012
  Purpose

A prospective, open, randomized trial, in which the investigators aim to achieve optimal immunosuppression after renal renal transplantation with maximal reduction of side effects, especially of vascular injury, chronic allograft nephropathy, osteoporosis and malignancies. Immunosuppression without steroids and CNI minimization is compared to standard immunosuppression, consisting of tacrolimus OD, mycophenolic acid and corticosteroids.


Condition Intervention Phase
Renal Insufficiency
Kidney Transplantation
Drug: tacrolimus OD, mycophenolic acid, prednisolone
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: Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • renal function parameters [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    renal function as measured by serum Creatinine and Creatinine Clearance, Nankivell GFR, proteinuria and microalbuminuria


Secondary Outcome Measures:
  • tubular atrophy and interstitial fibrosis [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    tubular atrophy and interstitial fibrosis in renal biopsies

  • rejection episodes [ Time Frame: two years ] [ Designated as safety issue: No ]
  • graft and patient survival [ Time Frame: two years ] [ Designated as safety issue: No ]
  • cardiovascular incidents [ Time Frame: two years ] [ Designated as safety issue: No ]
  • infectious complications [ Time Frame: two years ] [ Designated as safety issue: No ]
  • dexa bone densitometry [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: April 2011
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: standard immunosuupression
triple maintenance immunosuppression with tacrolimus OD (maintenance 6-10 ng/ml), mycophenolic acid 2 dd 540mg and prednisolone 7.5 mg
Drug: tacrolimus OD, mycophenolic acid, prednisolone
tacrolimus maintenance 6-10 ng/ml, in the low dose tacrolimus group after 6 months fixed dose reduction of 50% tacrolimus through levels will be 3-5 ng/ml mycophenolic acid 2 dd 720mg, after 2 weeks reduced to 2 dd 540 mg in all groups methylprednisolone 500, 250, 125 mg on day 0, 1, and 2 in all groups prednisolone 1 dd 10 mg, and from week 6 prednisolone 7.5 mg in the standard immunosuppression and low dose tacrolimus group No prednisolone will be given the steroid free group
Other Name: advagraf, mycophenolic acid
Experimental: steroidfree
maintenance immunosuppression with tacrolimus OD (target range 6-10 ng/ml), mycophenolic acid (2 dd 540 mg)
Drug: tacrolimus OD, mycophenolic acid, prednisolone
tacrolimus maintenance 6-10 ng/ml, in the low dose tacrolimus group after 6 months fixed dose reduction of 50% tacrolimus through levels will be 3-5 ng/ml mycophenolic acid 2 dd 720mg, after 2 weeks reduced to 2 dd 540 mg in all groups methylprednisolone 500, 250, 125 mg on day 0, 1, and 2 in all groups prednisolone 1 dd 10 mg, and from week 6 prednisolone 7.5 mg in the standard immunosuppression and low dose tacrolimus group No prednisolone will be given the steroid free group
Other Name: advagraf, mycophenolic acid
Experimental: low dose tacrolimus
triple maintenance immunosuppression with tacrolimus OD (maintenance 6-10 ng/ml), mycophenolic acid 2 dd 540mg and prednisolone 7.5 mg. After 6 months lowering of tacrolimus OD maintenance 3-5 ng/ml
Drug: tacrolimus OD, mycophenolic acid, prednisolone
tacrolimus maintenance 6-10 ng/ml, in the low dose tacrolimus group after 6 months fixed dose reduction of 50% tacrolimus through levels will be 3-5 ng/ml mycophenolic acid 2 dd 720mg, after 2 weeks reduced to 2 dd 540 mg in all groups methylprednisolone 500, 250, 125 mg on day 0, 1, and 2 in all groups prednisolone 1 dd 10 mg, and from week 6 prednisolone 7.5 mg in the standard immunosuppression and low dose tacrolimus group No prednisolone will be given the steroid free group
Other Name: advagraf, mycophenolic acid

Detailed Description:

Before transplantation 300 patients will be randomized 1:1:1 in three groups. Group 1 will be treated with basiliximab induction and a three day course of steroids followed by a steroid free maintenance regimen consisting of standard-dose tacrolimus OD and mycophenolic acid. Group 2 will be treated with Basiliximab induction followed by standard-dose tacrolimus OD, mycophenolic acid and steroids. Group 3 will be treated with basiliximab induction followed by standard-dose tacrolimus OD for six months, whereafter the dose will be reduced plus mycophenolic acid and steroids. The total study period will be 2 years. Primary endpoint will be renal function, proteinuria and microalbuminuria measured 6, 12, and 24 months after transplantation. Renal function will be measured by serum Creatinine, Creatinine clearances and Nankivell GFR (4). Secondary endpoints will be the degree of tubular atrophy and interstitial fibrosis and the degree of arteriolar hyalinosis in renal biopsies taken at 12 and 24 months after transplantation. Biopsies will be evaluated according to the Banff '07 Criteria for Renal Allograft Biopsy Interpretation (appendix II). Quantitative morphometric analysis of interstitial fibrous tissue will be performed using the digital image analysis technique. Other secondary endpoints are patient and graft survival, the incidence of allograft rejection, cardiovascular accidents, pulse wave velocity, blood pressure, the number of antihypertensives, lipid profile, the incidence of malignancies, the incidence of infectious complications, the incidence of post transplant diabetes mellitus and the development of osteoporosis.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • recipient of a kidney graft (first of second) from a deceased or living (non-HLA identical) donor

Exclusion Criteria:

  • patients with multi-organ transplants
  • patients who are receiving a third or fourth transplant
  • patients who have > 75% (current of historic) panel reactive antibodies
  • patients receiving a kidney from a HLA identical living donr
  • female patients who are pregnant or unwilling to used adequate contraception during the study
  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: NCT01560572

Contacts
Contact: Jan-Stephan Sanders, MD, PhD +31503616161 j.sanders@umcg.nl

Locations
Netherlands
Academisch Medisch Centrum Recruiting
Amsterdam, Netherlands
Contact: Frederike Bemelman, MD, PhD         
Principal Investigator: Frederike Bemelman, MD, PhD         
University Medical Center Groningen Recruiting
Groningen, Netherlands
Contact: Jan-Stephan Sanders, MD, PhD    +31503616161    j.sanders@umcg.nl   
Principal Investigator: Jan-Stephan Sanders, MD, PhD         
Leiden University Medical Center Recruiting
Leiden, Netherlands
Contact: Aiko de Vries, MD, PhD         
Principal Investigator: Aiko de Vries, MD, PhD         
Sponsors and Collaborators
University Medical Centre Groningen
Leiden University Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Jan-Stephan Sanders, MD, PhD University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: J.S.F. Sanders, principal investigator, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01560572     History of Changes
Other Study ID Numbers: Allegro
Study First Received: December 21, 2011
Last Updated: March 22, 2012
Health Authority: Netherlands: Independent Ethics Committee

Keywords provided by University Medical Centre Groningen:
kidney transplantation
immunosuppression
steroids
tacrolimus OD

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Immunosuppressive Agents
Mycophenolate mofetil
Tacrolimus
Basiliximab
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 22, 2014