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

University Medical Center Groningen (UMCG)

Status and phase: Completed; Phase 4

Conditions: Kidney Transplantation; Renal Insufficiency

Treatments: Drug: tacrolimus OD, mycophenolic acid, prednisolone

Study type: Interventional

Funder types: Other

Identifiers

NCT01560572

Allegro

Details and patient eligibility

About

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.

Full 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.

Enrollment: 305 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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305 participants in 3 patient groups

standard immunosuupression

Active Comparator group

Description:

triple maintenance immunosuppression with tacrolimus OD (maintenance 6-10 ng/ml), mycophenolic acid 2 dd 540mg and prednisolone 7.5 mg

Treatment:

Drug: tacrolimus OD, mycophenolic acid, prednisolone

steroidfree

Experimental group

Description:

maintenance immunosuppression with tacrolimus OD (target range 6-10 ng/ml), mycophenolic acid (2 dd 540 mg)

Treatment:

Drug: tacrolimus OD, mycophenolic acid, prednisolone

low dose tacrolimus

Experimental group

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

Treatment:

Drug: tacrolimus OD, mycophenolic acid, prednisolone