Steroid Free Immunosuppression or Calcineurin Inhibitor Minimization After Basiliximab Induction Therapy in Kidney Transplantation: Comparison With a Standard Quadruple Immunosuppressive Regimen (Allegro)
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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 |
- 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
- 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 |
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| Contact: Jan-Stephan Sanders, MD, PhD | +31503616161 | j.sanders@umcg.nl |
| 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 | |
| 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 May 23, 2013