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

Kidney Transplantation Clinical Trial

— Allegro  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01560572
• Other study ID #: Allegro
• Status: Completed
• Phase: Phase 4
• Start date: April 2011
• Est. completion date: April 2016

Study information

• Verified date: December 2021
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: April 2016
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplantation
• Renal Insufficiency

Intervention

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

Locations

Country	Name	City	State
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Center Groningen	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	renal function parameters	renal function as measured by serum Creatinine and Creatinine Clearance, CKD-EPI, proteinuria	24 months
Secondary	tubular atrophy and interstitial fibrosis	tubular atrophy and interstitial fibrosis in renal biopsies	24 months
Secondary	rejection episodes	number of treated biopsy proven acute rejection episodes (as scored by pathologist via Banff classification)	two years
Secondary	graft and patient survival	graft and patient survival	two years
Secondary	myocardial infarctions	number of myocardial infarctions	two years
Secondary	cerebrovascular accidents	number of cerebrovascular accidents	two years
Secondary	number of participants with infectious complications	bacterial and viral infections as measured by culture (bacterial infections) or PCR (viral infections)	two years
Secondary	number of participants with osteoporosis	as established by dexa bone densitometry	2 years