Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen (Allegro)
Primary Purpose
Renal Insufficiency, Kidney Transplantation
Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
tacrolimus OD, mycophenolic acid, prednisolone
Sponsored by
About this trial
This is an interventional treatment trial for Renal Insufficiency focused on measuring kidney transplantation, immunosuppression, steroids, tacrolimus OD
Eligibility 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
Sites / Locations
- Academisch Medisch Centrum
- University Medical Center Groningen
- Leiden University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
standard immunosuupression
steroidfree
low dose tacrolimus
Arm Description
triple maintenance immunosuppression with tacrolimus OD (maintenance 6-10 ng/ml), mycophenolic acid 2 dd 540mg and prednisolone 7.5 mg
maintenance immunosuppression with tacrolimus OD (target range 6-10 ng/ml), mycophenolic acid (2 dd 540 mg)
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
Outcomes
Primary Outcome Measures
renal function parameters
renal function as measured by serum Creatinine and Creatinine Clearance, CKD-EPI, proteinuria
Secondary Outcome Measures
tubular atrophy and interstitial fibrosis
tubular atrophy and interstitial fibrosis in renal biopsies
rejection episodes
number of treated biopsy proven acute rejection episodes (as scored by pathologist via Banff classification)
graft and patient survival
graft and patient survival
myocardial infarctions
number of myocardial infarctions
cerebrovascular accidents
number of cerebrovascular accidents
number of participants with infectious complications
bacterial and viral infections as measured by culture (bacterial infections) or PCR (viral infections)
number of participants with osteoporosis
as established by dexa bone densitometry
Full Information
NCT ID
NCT01560572
First Posted
December 21, 2011
Last Updated
December 20, 2021
Sponsor
University Medical Center Groningen
Collaborators
Leiden University Medical Center, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1. Study Identification
Unique Protocol Identification Number
NCT01560572
Brief Title
Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen
Acronym
Allegro
Official Title
Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen
Collaborators
Leiden University Medical Center, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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 24 months after transplantation. Renal function will be measured by serum Creatinine, Creatinine clearances and CKD-EPI. 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 Criteria for Renal Allograft Biopsy Interpretation. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Insufficiency, Kidney Transplantation
Keywords
kidney transplantation, immunosuppression, steroids, tacrolimus OD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
305 (Actual)
8. Arms, Groups, and Interventions
Arm Title
standard immunosuupression
Arm Type
Active Comparator
Arm Description
triple maintenance immunosuppression with tacrolimus OD (maintenance 6-10 ng/ml), mycophenolic acid 2 dd 540mg and prednisolone 7.5 mg
Arm Title
steroidfree
Arm Type
Experimental
Arm Description
maintenance immunosuppression with tacrolimus OD (target range 6-10 ng/ml), mycophenolic acid (2 dd 540 mg)
Arm Title
low dose tacrolimus
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
tacrolimus OD, mycophenolic acid, prednisolone
Other Intervention Name(s)
advagraf, mycophenolic acid
Intervention Description
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
Primary Outcome Measure Information:
Title
renal function parameters
Description
renal function as measured by serum Creatinine and Creatinine Clearance, CKD-EPI, proteinuria
Time Frame
24 months
Secondary Outcome Measure Information:
Title
tubular atrophy and interstitial fibrosis
Description
tubular atrophy and interstitial fibrosis in renal biopsies
Time Frame
24 months
Title
rejection episodes
Description
number of treated biopsy proven acute rejection episodes (as scored by pathologist via Banff classification)
Time Frame
two years
Title
graft and patient survival
Description
graft and patient survival
Time Frame
two years
Title
myocardial infarctions
Description
number of myocardial infarctions
Time Frame
two years
Title
cerebrovascular accidents
Description
number of cerebrovascular accidents
Time Frame
two years
Title
number of participants with infectious complications
Description
bacterial and viral infections as measured by culture (bacterial infections) or PCR (viral infections)
Time Frame
two years
Title
number of participants with osteoporosis
Description
as established by dexa bone densitometry
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan-Stephan Sanders, MD, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Academisch Medisch Centrum
City
Amsterdam
Country
Netherlands
Facility Name
University Medical Center Groningen
City
Groningen
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
12. IPD Sharing Statement
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Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen
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