Overview

This trial is active, not recruiting.

Conditions renal insufficiency, kidney transplantation
Treatment tacrolimus od, mycophenolic acid, prednisolone
Phase phase 4
Sponsor University Medical Centre Groningen
Collaborator Leiden University Medical Center
Start date April 2011
End date April 2015
Trial size 300 participants
Trial identifier NCT01560572, Allegro

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
triple maintenance immunosuppression with tacrolimus OD (maintenance 6-10 ng/ml), mycophenolic acid 2 dd 540mg and prednisolone 7.5 mg
tacrolimus od, mycophenolic acid, prednisolone advagraf, mycophenolic acid
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
(Experimental)
maintenance immunosuppression with tacrolimus OD (target range 6-10 ng/ml), mycophenolic acid (2 dd 540 mg)
tacrolimus od, mycophenolic acid, prednisolone advagraf, mycophenolic acid
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
(Experimental)
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
tacrolimus od, mycophenolic acid, prednisolone advagraf, mycophenolic acid
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 Outcomes

Measure
renal function parameters
time frame: 24 months

Secondary Outcomes

Measure
tubular atrophy and interstitial fibrosis
time frame: 24 months
rejection episodes
time frame: two years
graft and patient survival
time frame: two years
cardiovascular incidents
time frame: two years
infectious complications
time frame: two years
dexa bone densitometry
time frame: 2 years

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

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

Additional Information

Official title Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen
Principal investigator Jan-Stephan Sanders, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2014.
Information provided to ClinicalTrials.gov by University Medical Centre Groningen.