Standard Versus Prolonged-release Tacrolimus Monotherapy After Alemtuzumab Induction in Kidney Transplantation

Study Overview
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Brief Summary
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The current anti-rejection drug regime for kidney transplant recipients in use at the West London Renal & Transplant Centre (WLRaTC) consists of induction therapy with the very potent monoclonal antibody Campath 1-H (Alemtuzumab) followed by long-term maintenance with the Calcineurin inhibitor Tacrolimus The recent development (and licensing in the UK) of an extended-release, once daily formulation of Tacrolimus holds out the promise of simpler drug regimes for our patients. In the context of our current successful use of Tacrolimus monotherapy maintenance after Campath 1-H induction, the extended-release Tacrolimus formulation will enable us to offer a regime where the only long-term immunosuppressive treatment that most of our patients need will be a single drug, taken once a day. The investigators wish to assess the efficacy of such a regime in a structured comparison with our current protocol.

Detailed Description
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Purpose of Study: The current immunosuppressive regime used as anti-rejection therapy after kidney transplantation in the West London Renal & Transplant Centre at Imperial College Healthcare NHS Trust consists of induction therapy with Campath 1-H(Alemtuzumab) and a 1 week course of steroids followed by maintenance mono-therapy with standard-release (twice daily) Tacrolimus (Prograf). This study is designed to compare the costs and outcomes of this regime with one in which extended-release (once daily) Tacrolimus (Advagraf) is used in place of the standard-release Tacrolimus. Study Type: Phase IV Study Design: Prospective, randomised, controlled, open study. Patients will be randomized 1:1 between the standard and extended-release Tacrolimus arms. Study entry will be stratified by live donor vs deceased donor transplants. The total recruitment target is 100 patients (50 standard release/50 extended release). Study Description: Patients will be randomised to receive either Prograf or Advagraf prior to transplantation. Other than through the taking of extra blood samples at the time of routine clinical visits, participants will receive identical in-patient and out-patient management to patients undergoing kidney transplantation under our standard protocol. Patients in the study will be asked to complete a short Health-Related Quality of Life questionnaire (SF-36) before transplantation and at 1 year post transplant. They will also be asked to complete a Medication Adherence Rating Score at 3, 6, and 12 months post-transplant.

Official Title
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A Phase-IV Study Comparing Standard Release Tacrolimus (Prograf) vs Prolonged-release Tacrolimus (Advagraf) Monotherapy as Maintenance Immunosuppression After Induction With Alemtuzumab in Kidney Transplantation

Conditions
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End-stage Renal Failure, Graft Rejection

Intervention / Treatment
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* Drug: Tacrolimus (Kidney transplant maintenance immunosuppression)
* Drug: Kidney transplant maintenance immunosuppression


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Live donor kidney transplant recipients heart-beating-Deceased donor kidney transplant recipients Patients suitable for induction therapy with Alemtuzumab Exclusion Criteria: Recipients of Non-heart-beating deceased donor kidney transplants Recipients of simultaneous kidney/pancreas transplants ABO incompatible/desensitized transplant recipients Positive flow cross-match/desensitized transplant recipients Patients with heavy prior exposure to myelosuppressive therapy Patients with previous malignancy Patients with HIV,Hepatitis-C, or Hepatitis-B infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolonged-Release Tacrolimus<br>Transplant maintenance immunosuppression with Prolonged-release Tacrolimus monotherapy | Drug: Kidney transplant maintenance immunosuppression<br>* Prolonged-release Tacrolimus 1 to 20mg daily in a single am dose adjusted to trough drug levels 6-9ng/ml<br>* Other names: Advagraf;|
| Active Comparator: Standard-Release tacrolimus<br>Transplant maintenance immunosuppression with Standard-release Tacrolimus monotherapy | Drug: Tacrolimus (Kidney transplant maintenance immunosuppression)<br>* Standard-release Tacrolimus 1 to 20mg daily in two divided doses to maintain trough drug levels 6-9ng/ml<br>* Other names: Prograf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Survival With a Functioning Graft |  | One year post kidney transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rejection-free Patient Survival With a Functioning Graft |  | One and two years post kidney transplantation | 
| Patient-reported Quality of Life, and Medication Adherence |  | 3,6,& 12 months post kidney transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplant, Rejection, Adherence, Quality of life